| Revision as of 17:12, 12 February 2012 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{drugbox}} (changes to verified fields - updated 'ChemSpiderID_Ref', 'UNII_Ref', 'ChEBI_Ref', 'KEGG_Ref', 'StdInChI_Ref', 'StdInChIKey_Ref', 'CAS_number_Ref') per Chem/Drugbox validation (report [[Misplaced Pages talk:WikiProj...← Previous edit | Latest revision as of 19:04, 2 October 2024 edit undoCitation bot (talk | contribs)Bots5,431,802 edits Added bibcode. | Use this bot. Report bugs. | Suggested by Dominic3203 | Category:Genes on human chromosome 11 | #UCB_Category 260/942 | ||
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| {{cs1 config|name-list-style=vanc}} | |||
| {{PBB|geneid=51083}} | |||
| {{Infobox_gene}} | |||
| {{Drugbox | {{Drugbox | ||
| | Verifiedfields = changed | | Verifiedfields = changed | ||
| | Watchedfields = changed | |||
| | verifiedrevid = 403760667 | | verifiedrevid = 403760667 | ||
| | IUPAC_name = |
| IUPAC_name = | ||
| | image = |
| image = | ||
| | alt = |
| alt = | ||
| <!-- Clinical data --> | |||
| | tradename = | |||
| <!--Clinical data--> | |||
| | tradename = | |||
| | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | ||
| | pregnancy_US = <!-- A / B / C / D / X --> | | pregnancy_US = <!-- A / B / C / D / X --> | ||
| | pregnancy_category = |
| pregnancy_category = | ||
| | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> | | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> | ||
| | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | ||
| | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --> | | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --> | ||
| | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | ||
| | legal_status = |
| legal_status = | ||
| | routes_of_administration = |
| routes_of_administration = | ||
| <!-- Pharmacokinetic data --> | |||
| | bioavailability = | |||
| <!--Pharmacokinetic data--> | |||
| | protein_bound = | |||
| | bioavailability = | |||
| | |
| metabolism = | ||
| | elimination_half-life = | |||
| | metabolism = | |||
| | excretion = | |||
| | elimination_half-life = | |||
| <!-- Identifiers --> | |||
| | excretion = | |||
| | CAS_number_Ref = {{cascite|changed|??}} | |||
| | CAS_number = 88813-36-9 | |||
| <!--Identifiers--> | |||
| | ATCvet = | |||
| | CAS_number_Ref = {{cascite|correct|??}} | |||
| | CAS_number = | |||
| | ATCvet = | |||
| | ATC_prefix = <!-- 'none' if uncategorised --> | | ATC_prefix = <!-- 'none' if uncategorised --> | ||
| | ATC_suffix = |
| ATC_suffix = | ||
| | PubChem = |
| PubChem = | ||
| | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | ||
| | DrugBank = |
| DrugBank = | ||
| | ChEMBL_Ref = {{ebicite|correct|EBI}} | | ChEMBL_Ref = {{ebicite|correct|EBI}} | ||
| | ChEMBL = 501079 | | ChEMBL = 501079 | ||
| | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ||
| | ChemSpiderID = |
| ChemSpiderID = none | ||
| <!-- Chemical data --> | |||
| | C=146 | H=213 | N=43 | O=40 | |||
| <!--Chemical data--> | |||
| | chemical_formula = C146 H213 N43 O40 | |||
| | molecular_weight = 3210.5 | |||
| }} | }} | ||
| '''Galanin''' is a ] encoded by the ''GAL'' ],<ref name="pmid7508413"/> that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three ].<ref name="receptors"/> | '''Galanin''' is a ] encoded by the ''GAL'' ],<ref name="pmid7508413"/> that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three ].<ref name="receptors"/> | ||
| Much of galanin's functional role is still undiscovered. Galanin is closely involved in the modulation and inhibition of ] in ]. Galanin has been implicated in many biologically diverse functions, including: ], waking and sleep regulation, cognition, feeding, regulation of mood, regulation of blood pressure, it also has roles in development as well as acting as a ].<ref name="pmid18500643"/> Galanin neurons in the ] of the hypothalamus may govern parental behaviour.<ref name="pmid24828191"/> Galanin is linked to a number of diseases including ], ] as well as ], ], ], and ].<ref name="pmid16052044"/><ref name="pmid15944034"/> Galanin appears to have ] activity as its biosynthesis is increased 2-10 fold upon ] in the ] as well as when seizure activity occurs in the brain. It may also promote ].<ref name="receptors"/> | |||
| Galanin is predominantly an inhibitory, ] neuropeptide<ref name="neuroscience"/> and as such inhibits ] release. Galanin is often co-localized with classical neurotransmitters such as ], ], and ], and also with other neuromodulators such as ], ], and ].<ref name = "acnp"/> | Galanin is predominantly an inhibitory, ] neuropeptide<ref name="neuroscience"/> and as such inhibits ] release. Galanin is often co-localized with classical neurotransmitters such as ], ], and ], and also with other neuromodulators such as ], ], and ].<ref name = "acnp"/> | ||
| ==Discovery== | ==Discovery== | ||
| Galanin was first identified from porcine intestinal extracts in 1978 by Professor Viktor Mutt and colleagues at the Karolinska Institute, Sweden<ref name="MFN"/> using a chemical assay technique that detects peptides according to its C-terminal alanine amide structure. Galanin is so-called because it contains an N-terminal glycine residue and a C-terminal alanine.<ref name="History"/> The structure of galanin was determined in 1983 by the same team, and |
Galanin was first identified from porcine intestinal extracts in 1978 by Professor Viktor Mutt and colleagues at the ], Sweden<ref name="MFN"/> using a chemical assay technique that detects peptides according to its C-terminal alanine amide structure. Galanin is so-called because it contains an N-terminal glycine residue and a C-terminal alanine.<ref name="History"/> The structure of galanin was determined in 1983 by the same team, and the ] of galanin was cloned from a rat ] library in 1987.<ref name = "MFN"/> | ||
| ==Tissue distribution== | ==Tissue distribution== | ||
| Galanin is located predominantly in the central nervous system and ]. Within the central nervous system, highest concentrations are found in the ], with lower levels in the ] and ]. In the hypothalamus, it is for example found in the ] where it has sleep-promoting function. Within the brain, galanin has also been found in the ventral ] and ].<ref name="Kuteeva_2010">{{cite journal | vauthors = Kuteeva E, Hökfelt T, Wardi T, Ogren SO | journal = Experientia Supplementum (2012) | series = Experientia Supplementum | title = Galanin, galanin receptor subtypes and depression-like behaviour | volume = 102 | pages = 163–181 | date = 2010 | pmid = 21299068 | doi = 10.1007/978-3-0346-0228-0_12 | publisher = Springer | isbn = 978-3-0346-0227-3 | veditors = Hökfelt T }}</ref> Along with this, the immune reaction of galanin in the brain is centered in the hypothalamopituitary.<ref>{{cite journal | vauthors = Ch'ng JL, Christofides ND, Anand P, Gibson SJ, Allen YS, Su HC, Tatemoto K, Morrison JF, Polak JM, Bloom SR | display-authors = 6 | title = Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury | journal = Neuroscience | volume = 16 | issue = 2 | pages = 343–354 | date = October 1985 | pmid = 2417156 | doi = 10.1016/0306-4522(85)90007-7 | s2cid = 32774212 }}</ref> Gastrointestinal galanin is most abundant in the ], with lower concentrations in the stomach, small intestine, and colon.<ref name="pmid2448788"/> Galanin is also expressed in the skin where is serves anti-inflammatory functions.<ref name="Bauer_2010">{{cite journal | vauthors = Bauer JW, Lang R, Jakab M, Kofler B | journal = Experientia Supplementum (2012) | series = Experientia Supplementum | title = Galanin family of peptides in skin function | volume = 102 | pages = 51–59 | date = 2010 | pmid = 21299061 | doi = 10.1007/978-3-0346-0228-0_5 | publisher = Springer | isbn = 978-3-0346-0227-3 | veditors = Hökfelt T }}</ref> Specifically, it has been found in ]s, ]s, and around blood vessels.<ref name="Bauer_2010" /> Galanin has been found in ]s.<ref name="Mitsukawa_2010">{{cite journal | vauthors = Mitsukawa K, Lu X, Bartfai T | journal = Experientia Supplementum (2012) | series = Experientia Supplementum | title = Galanin, galanin receptors, and drug targets | volume = 102 | pages = 7–23 | date = 2010 | pmid = 21299058 | doi = 10.1007/978-3-0346-0228-0_2 | publisher = Springer | isbn = 978-3-0346-0227-3 | veditors = Hökfelt T }}</ref> Within gastric cancer cells, galanin has been found to have a ] role, but hypermethylation has been shown to stop its tumor suppressive properties.<ref>{{cite journal | vauthors = Yoon D, Bae K, Lee MK, Kim JH, Yoon KA | title = Galanin is an epigenetically silenced tumor suppressor gene in gastric cancer cells | journal = PLOS ONE | volume = 13 | issue = 2 | pages = e0193275 | date = 2018-02-20 | pmid = 29462183 | pmc = 5819827 | doi = 10.1371/journal.pone.0193275 | veditors = Suzuki H | doi-access = free | bibcode = 2018PLoSO..1393275Y }}</ref> | |||
| Galanin is located predominantly in the central nervous system and gastrointestinal tract. Within the central nervous system, highest concentrations are found in the ], with lower levels in the ] and ]. Gastrointestinal galanin is most abundant in the ], with lower concentrations in the stomach, small intestine, and colon.<ref name="pmid2448788"/> | |||
| ==Structure== | == Structure == | ||
| {| class="wikitable" border="1" align=" |
{| class="wikitable" border="1" align="right" | ||
| |+Endogenously occurring galanin sequences | |+Endogenously occurring galanin sequences | ||
| |- | |- | ||
| Line 77: | Line 73: | ||
| | G W T L N || S A G Y L || L G P H A || I D N H R || S F '''S''' D K || '''H''' G L '''T'''* | | G W T L N || S A G Y L || L G P H A || I D N H R || S F '''S''' D K || '''H''' G L '''T'''* | ||
| |- | |- | ||
| |colspan=7 align=center| <small>* C-terminal amide ** C-terminal free acid</small> | | colspan=7 align=center| <small>* C-terminal amide ** C-terminal free acid</small> | ||
| |} | |} | ||
| Galanin is a ] consisting of a chain of 29 ] (30 amino acids in humans) produced from the cleavage of a 123-amino acid protein known as |
Galanin is a ] consisting of a chain of 29 ] (30 amino acids in humans) produced from the cleavage of a 123-amino acid protein known as prepro galanin, which is encoded by the ''GAL'' gene.<ref name="pmid7508413"/> The sequence of this gene is highly conserved among mammals, showing over 85% ] between rat, mouse, porcine, bovine, and human sequences.<ref name = "acnp"/> In these animal forms, the first 15 amino acids from the ] are identical, but amino acids differ at several positions on the ] end of the protein. | ||
| These slight differences in protein structure have far-reaching implications on their function. For example, porcine and rat galanin inhibit glucose-induced ] secretion in rats and dogs but have no effect on insulin secretion in humans. This demonstrates that it is essential to study the effects of galanin |
These slight differences in protein structure have far-reaching implications on their function. For example, porcine and rat galanin inhibit glucose-induced ] secretion in rats and dogs but have no effect on insulin secretion in humans. This demonstrates that it is essential to study the effects of galanin and other regulatory peptides in their autologous species.<ref name="pmid1710578"/> | ||
| The galanin family of protein consists of four proteins, of which GAL was the first to be identified. The second was galanin message-associated protein (GMAP), a 59- or 60-amino acid peptide also formed from the cleavage of |
The galanin family of protein consists of four proteins, of which GAL was the first to be identified. The second was galanin message-associated protein (GMAP), a 59- or 60-amino acid peptide also formed from the cleavage of prepro galanin.<ref name="History"/> The other two peptides, ] (GALP) and alarin, were identified relatively recently and are both encoded for in the same gene, the prepro GALP gene. GALP and alarin are produced by different post-transcriptional ] of this gene.<ref name="overview"/> | ||
| {| align="center" | |||
| {| | |||
| |{{Infobox protein family | |{{Infobox protein family | ||
| | Symbol = Galanin | | Symbol = Galanin | ||
| Line 107: | Line 103: | ||
| | Symbol = GMAP | | Symbol = GMAP | ||
| | Name = Galanin message associated peptide (GMAP) | | Name = Galanin message associated peptide (GMAP) | ||
| | image = |
| image = | ||
| | width = |
| width = | ||
| | caption = |
| caption = | ||
| | Pfam = PF06540 | | Pfam = PF06540 | ||
| | Pfam_clan = |
| Pfam_clan = | ||
| | InterPro = IPR013068 | | InterPro = IPR013068 | ||
| | SMART = |
| SMART = | ||
| | PROSITE = |
| PROSITE = | ||
| | MEROPS = |
| MEROPS = | ||
| | SCOP = |
| SCOP = | ||
| | TCDB = |
| TCDB = | ||
| | OPM family = |
| OPM family = | ||
| | OPM protein = |
| OPM protein = | ||
| | CAZy = |
| CAZy = | ||
| | CDD = |
| CDD = | ||
| }} | }} | ||
| |} | |} | ||
| Line 127: | Line 123: | ||
| ==Receptors== | ==Receptors== | ||
| Galanin signalling occurs through three classes of receptors, ], ], and ], which are all part of the ] (GPCR) superfamily. Galanin receptors are expressed in the ], in the ], and on ]s. The level of expression of the different receptors varies at each location, and this distribution changes after injury to neurons.<ref name="receptors"/> |
Galanin signalling occurs through three classes of receptors, ], ], and ], which are all part of the ] (GPCR) superfamily. Galanin receptors are expressed in the ], in the ], and on ]s. The level of expression of the different receptors varies at each location, and this distribution changes after injury to neurons.<ref name="receptors"/> Experiments into the function of the receptor subtypes involve mostly ] mice. The location of the receptor and the combination of receptors that are inhibited or stimulated heavily affect the outcome of galanin signalling.<ref name="receptors"/> | ||
| ==Clinical characteristics== | ==Clinical characteristics== | ||
| ===Alzheimer’s Disease=== | |||
| ===Appetite=== | |||
| One of the ] features of the brain in the later stages of ] is the presence of overgrown GAL-containing fibres innervating the surviving ] neurons.<ref name="pmid18500641"/> Another feature is an increase in the expression of GAL and GAL receptors, in which increases of up to 200% have been observed in post-mortem brains of Alzheimer’s patients.<ref name="receptors"/><ref name="overview"/> The cause and role of this increase is poorly understood.<ref name="pmid18500641"/><ref name="pmid14993421"/> | |||
| Injections of galanin into the ] or directly into the hypothalamus creates the urge to feed, with a preference for eating fats.<ref name="Mitsukawa_2010" /> Galanin also regulates glucose metabolism and can potentially alleviate symptoms of ] due to its interaction with insulin resistance.<ref name="Fang_2020">{{cite journal | vauthors = Fang P, Yu M, Shi M, Bo P, Zhang Z | title = Galanin peptide family regulation of glucose metabolism | journal = Frontiers in Neuroendocrinology | volume = 56 | pages = 100801 | date = January 2020 | pmid = 31705911 | doi = 10.1016/j.yfrne.2019.100801 | doi-access = free }}</ref> Galanin is an inhibitor of pancreatic secretion of insulin.<ref name="Mitsukawa_2010" /> | |||
| === Addiction === | |||
| Galanin plays a role in addiction regulation.<ref name="Genders_2020">{{cite journal | vauthors = Genders SG, Scheller KJ, Djouma E | title = Neuropeptide modulation of addiction: Focus on galanin | journal = Neuroscience and Biobehavioral Reviews | volume = 110 | pages = 133–149 | date = March 2020 | pmid = 29949733 | doi = 10.1016/j.neubiorev.2018.06.021 | s2cid = 49486365 }}</ref> It is involved in repeated alcohol intake.<ref name="Mitsukawa_2010" /> Along with addiction to alcohol, galanin has been shown to play a role in addiction to ] and opiates.<ref name="Genders_2020" /> | |||
| ===Alzheimer's disease=== | |||
| One of the ] features of the brain in the later stages of ] is the presence of overgrown GAL-containing fibres innervating the surviving ] neurons.<ref name="pmid18500641"/> Another feature is an increase in the expression of GAL and GAL receptors, in which increases of up to 200% have been observed in postmortem brains of Alzheimer's patients.<ref name="receptors"/><ref name="overview"/> The cause and role of this increase is poorly understood.<ref name="pmid18500641"/><ref name="pmid14993421"/> | |||
| It has been suggested that the hyper-innervation acts to promote the death of these neurons and that the inhibitory effect of galanin on cholinergic neurons worsened the degeneration of ] function in patients by decreasing the amount of ] available to these neurons.<ref name= "receptors"/><ref name="pmid18500641"/> | It has been suggested that the hyper-innervation acts to promote the death of these neurons and that the inhibitory effect of galanin on cholinergic neurons worsened the degeneration of ] function in patients by decreasing the amount of ] available to these neurons.<ref name= "receptors"/><ref name="pmid18500641"/> | ||
| A second hypothesis has been generated based on data that suggest GAL is involved in protecting the hippocampus from ] damage and the neurons in the cholinergic basal forebrain from ] toxicity.<ref name="pmid16246567"/> |
A second hypothesis has been generated based on data that suggest GAL is involved in protecting the hippocampus from ] damage and the neurons in the cholinergic ] from ] toxicity.<ref name="pmid16246567"/> | ||
| === Cognitive performance === | |||
| Galanin participates in cognitive performance and has been shown to weaken learning and cognition.<ref name="Mitsukawa_2010" /> | |||
| === Depression === | |||
| ] and ], two neurotransmitters involved in depression, are both co-expressed and modulated by galanin, suggesting that galanin plays a role in the regulation of depression.<ref name="Kuteeva_2010" /> Stimulation of the Gal1 and Gal3 receptors result in depression-like behaviors, whereas stimulation of the Gal2 receptor results in reduced depression-like behaviors.<ref name="Kuteeva_2010" /> Currently, one of the potential mechanisms for this is that galanin stimulates the hypothalamus-pituitary-adrenal axis, which leads to an increase in ] secretion.<ref name="Kuteeva_2010" /> Increased levels of glucocorticoid hormones is common in those who suffer from depression.<ref>{{cite journal | vauthors = Anacker C, Zunszain PA, Carvalho LA, Pariante CM | title = The glucocorticoid receptor: pivot of depression and of antidepressant treatment? | journal = Psychoneuroendocrinology | volume = 36 | issue = 3 | pages = 415–425 | date = April 2011 | pmid = 20399565 | pmc = 3513407 | doi = 10.1016/j.psyneuen.2010.03.007 }}</ref> | |||
| ===Endocrine=== | |||
| Galanin inhibits the secretion of ] and ] and stimulates the secretion of ], ], ], ], ], foliculotropin, ], hypothalamic ], and ].<ref>{{cite journal | vauthors = Zdrojewicz Z, Sowińska E, Sztuka-Pietkiewicz A | title = | journal = Endokrynologia, Diabetologia I Choroby Przemiany Materii Wieku Rozwojowego | volume = 6 | issue = 2 | pages = 129–134 | date = 2000 | pmid = 12818074 | url = https://pubmed.ncbi.nlm.nih.gov/12818074/ | access-date = 28 January 2023 }}</ref> | |||
| ===Epilepsy=== | ===Epilepsy=== | ||
| Galanin in the ] is an inhibitor of ] but not ] |
Galanin in the ] is an inhibitor of ] but not of ]. This means that galanin is capable of increasing the ]<ref name= "receptors"/> and, therefore, is expected to act as an ]. To be specific, GalR1 has been linked to the suppression of spontaneous seizures.<ref name="pmid15350653"/><ref name="pmid19199479"/> An agonist antiepileptic drug candidate is NAX 5055.<ref name="pmid19053761"/><ref name="pmid19332332"/> | ||
| ===In development=== | ===In development=== | ||
| It has been shown that galanin plays a role in the control of the early post-natal ] of the ] (DRG).<ref name="MFN"/> Galanin-mutant animals show a 13% decrease in the number of adult DRG cells as well as a 24% decrease in the percentage of cells expressing ]. This suggests that the cell loss by ] that usually occurs in the developing DRG is regulated by galanin and that the absence of galanin results in an increase in the number of cells that die. | It has been shown that galanin plays a role in the control of the early post-natal ] of the ] (DRG).<ref name="MFN"/> Galanin-mutant animals show a 13% decrease in the number of adult DRG cells as well as a 24% decrease in the percentage of cells expressing ]. This suggests that the cell loss by ] that usually occurs in the developing DRG is regulated by galanin and that the absence of galanin results in an increase in the number of cells that die. | ||
| === Pain and neuroprotection === | |||
| ===After injury=== | |||
| Galanin plays an inhibitory role in pain processing,<ref name="Hobson_2010">{{cite journal | vauthors = Hobson SA, Bacon A, Elliot-Hunt CR, Holmes FE, Kerr NC, Pope R, Vanderplank P, Wynick D | journal = Experientia Supplementum (2012) | series = Experientia Supplementum | display-authors = 6 | title = Galanin acts as a trophic factor to the central and peripheral nervous systems | volume = 102 | pages = 25–38 | date = 2010 | pmid = 21299059 | doi = 10.1007/978-3-0346-0228-0_3 | publisher = Springer | isbn = 978-3-0346-0227-3 | veditors = Hökfelt T }}</ref> with high doses having been shown to reduce pain.<ref name="Mitsukawa_2010" /> When galanin is added to the spinal cord, ] is reduced.<ref name="Xu_2010">{{cite journal | vauthors = Xu XJ, Hökfelt T, Wiesenfeld-Hallin Z | journal = Experientia Supplementum (2012) | series = Experientia Supplementum | title = Galanin and spinal pain mechanisms: past, present, and future | volume = 102 | pages = 39–50 | date = 2010 | pmid = 21299060 | doi = 10.1007/978-3-0346-0228-0_4 | publisher = Springer | isbn = 978-3-0346-0227-3 | veditors = Hökfelt T }}</ref> Along with this, galanin is believed to be effective in reducing spinal hyperexcitability.<ref name="Xu_2010" /> Sensory neurons increasingly release galanin when they are damaged.<ref name="Xu_2010" /> An increase in the concentrations of galanin are also believed to be for ] reasons and lead to promoted ].<ref name="Mitsukawa_2010" /> GalR2 activation is believed to mediate the survival role galanin plays in the ].<ref name="Hobson_2010" /> | |||
| ''In vitro'' experiments show that DRG cells removed from galanin mutants have impaired abilities to extend ] in culture, in that the number of cells producing neurites is decreased by a third and the mean length of these processes was halved when compared to wild-type controls. ''In vivo'', many of the actions of galanin in the brain after an injury are similar to those observed in the developing DRG. Adult mutant animals have been shown to be 35% less capable of regenerating the ] after crush injury, which is linked to long-term functional problems. | |||
| ===Parental role in mice=== | |||
| ==See also== | |||
| Galanin-expressing neurons in the medial preoptic area of the brain are responsible for regulating aggression towards pups by male mice.<ref name="pmid24828191"/> | |||
| * ] | |||
| Galanin-expressing neurons in the medial preoptic area are remodelled during pregnancy. Estrogen and progesterone genomic receptors in galanin (Gal)-expressing neurons control discrete aspected of plasticity.<ref>{{cite journal | vauthors = Ammari R, Monaca F, Cao M, Nassar E, Wai P, Del Grosso NA, Lee M, Borak N, Schneider-Luftman D, Kohl J | display-authors = 6 | title = Hormone-mediated neural remodeling orchestrates parenting onset during pregnancy | journal = Science | volume = 382 | issue = 6666 | pages = 76–81 | date = October 2023 | pmid = 37797007 | pmc = 7615220 | doi = 10.1126/science.adi0576 | bibcode = 2023Sci...382...76A }}</ref> | |||
| ==References== | |||
| {{Reflist|2|refs= | |||
| == See also == | |||
| <ref name="pmid7508413">{{cite journal | author = Evans H, Baumgartner M, Shine J, Herzog H | title = Genomic organization and localization of the gene encoding human preprogalanin | journal = Genomics | volume = 18 | issue = 3 | pages = 473–7 | year = 1993 | month = December | pmid = 7508413 | doi =10.1016/S0888-7543(11)80002-9 | url = | issn = }}</ref> | |||
| * ] | |||
| == References == | |||
| <ref name="receptors">{{cite journal | author = Mitsukawa K, Lu X, Bartfai T | title = Galanin, galanin receptors and drug targets | journal = Cell. Mol. Life Sci. | volume = 65 | issue = 12 | pages = 1796–805 | year = 2008 | month = June | pmid = 18500647 | doi = 10.1007/s00018-008-8153-8 | url = | issn = }}</ref> | |||
| {{Reflist|refs= | |||
| <ref name=" |
<ref name="pmid7508413">{{cite journal | vauthors = Evans H, Baumgartner M, Shine J, Herzog H | title = Genomic organization and localization of the gene encoding human preprogalanin | journal = Genomics | volume = 18 | issue = 3 | pages = 473–477 | date = December 1993 | pmid = 7508413 | doi = 10.1016/S0888-7543(11)80002-9 }}</ref> | ||
| <ref name |
<ref name="receptors">{{cite journal | vauthors = Mitsukawa K, Lu X, Bartfai T | title = Galanin, galanin receptors and drug targets | journal = Cellular and Molecular Life Sciences | volume = 65 | issue = 12 | pages = 1796–1805 | date = June 2008 | pmid = 18500647 | doi = 10.1007/s00018-008-8153-8 | s2cid = 263470319 | pmc = 11131746 }}</ref> | ||
| <ref name=" |
<ref name="neuroscience">{{cite journal | vauthors = Ito M | title = Functional roles of neuropeptides in cerebellar circuits | journal = Neuroscience | volume = 162 | issue = 3 | pages = 666–672 | date = September 2009 | pmid = 19361475 | doi = 10.1016/j.neuroscience.2009.01.019 | s2cid = 207245197 }}</ref> | ||
| <ref name=" |
<ref name="acnp">{{cite web| vauthors = Bartfai T |title=Galanin – A neuropeptide with important central nervous system actions |year=2000 |url=http://www.acnp.org/g4/GN401000054/CH054.html |access-date=November 19, 2009 |url-status=dead |archive-url=https://web.archive.org/web/20101202155619/http://www.acnp.org/g4/GN401000054/CH054.html |archive-date=December 2, 2010 }}</ref> | ||
| <ref name=" |
<ref name="MFN">{{cite journal | vauthors = Wynick D, Thompson SW, McMahon SB | title = The role of galanin as a multi-functional neuropeptide in the nervous system | journal = Current Opinion in Pharmacology | volume = 1 | issue = 1 | pages = 73–77 | date = February 2001 | pmid = 11712539 | doi = 10.1016/S1471-4892(01)00006-6 }}</ref> | ||
| <ref name=" |
<ref name="History">{{cite journal | vauthors = Hökfelt T, Tatemoto K | title = Galanin--25 years with a multitalented neuropeptide | journal = Cellular and Molecular Life Sciences | volume = 65 | issue = 12 | pages = 1793–1795 | date = June 2008 | pmid = 18500648 | doi = 10.1007/s00018-008-8152-9 | s2cid = 19878753 | pmc = 11131681 }}</ref> | ||
| <ref name=" |
<ref name="pmid24828191">{{cite journal | vauthors = Wu Z, Autry AE, Bergan JF, Watabe-Uchida M, Dulac CG | title = Galanin neurons in the medial preoptic area govern parental behaviour | journal = Nature | volume = 509 | issue = 7500 | pages = 325–330 | date = May 2014 | pmid = 24828191 | pmc = 4105201 | doi = 10.1038/nature13307 | bibcode = 2014Natur.509..325W }}</ref> | ||
| <ref name=" |
<ref name="pmid1710578">{{cite journal | vauthors = Bersani M, Johnsen AH, Højrup P, Dunning BE, Andreasen JJ, Holst JJ | title = Human galanin: primary structure and identification of two molecular forms | journal = FEBS Letters | volume = 283 | issue = 2 | pages = 189–194 | date = June 1991 | pmid = 1710578 | doi = 10.1016/0014-5793(91)80585-Q | s2cid = 19148582 | doi-access = free | bibcode = 1991FEBSL.283..189B }}</ref> | ||
| <ref name="pmid19199479">{{cite journal | vauthors = Zhang L, Robertson CR, Green BR, Pruess TH, White HS, Bulaj G | title = Structural requirements for a lipoamino acid in modulating the anticonvulsant activities of systemically active galanin analogues | journal = Journal of Medicinal Chemistry | volume = 52 | issue = 5 | pages = 1310–1316 | date = March 2009 | pmid = 19199479 | pmc = 2765488 | doi = 10.1021/jm801397w }}</ref> | |||
| <ref name=" |
<ref name="pmid19053761">{{cite journal | vauthors = Bulaj G, Green BR, Lee HK, Robertson CR, White K, Zhang L, Sochanska M, Flynn SP, Scholl EA, Pruess TH, Smith MD, White HS | display-authors = 6 | title = Design, synthesis, and characterization of high-affinity, systemically-active galanin analogues with potent anticonvulsant activities | journal = Journal of Medicinal Chemistry | volume = 51 | issue = 24 | pages = 8038–8047 | date = December 2008 | pmid = 19053761 | doi = 10.1021/jm801088x }}</ref> | ||
| <ref name="overview">{{cite journal | vauthors = Lang R, Gundlach AL, Kofler B | title = The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease | journal = Pharmacology & Therapeutics | volume = 115 | issue = 2 | pages = 177–207 | date = August 2007 | pmid = 17604107 | doi = 10.1016/j.pharmthera.2007.05.009 }}</ref> | |||
| <ref name=" |
<ref name="pmid19332332">{{cite journal | vauthors = White HS, Scholl EA, Klein BD, Flynn SP, Pruess TH, Green BR, Zhang L, Bulaj G | display-authors = 6 | title = Developing novel antiepileptic drugs: characterization of NAX 5055, a systemically-active galanin analog, in epilepsy models | journal = Neurotherapeutics | volume = 6 | issue = 2 | pages = 372–380 | date = April 2009 | pmid = 19332332 | pmc = 4402707 | doi = 10.1016/j.nurt.2009.01.001 }}</ref> | ||
| <ref name=" |
<ref name="pmid14993421">{{cite journal | vauthors = Counts SE, Perez SE, Ginsberg SD, De Lacalle S, Mufson EJ | title = Galanin in Alzheimer disease | journal = Molecular Interventions | volume = 3 | issue = 3 | pages = 137–156 | date = May 2003 | pmid = 14993421 | doi = 10.1124/mi.3.3.137 }}</ref> | ||
| <ref name=" |
<ref name="pmid18500641">{{cite journal | vauthors = Counts SE, Perez SE, Mufson EJ | title = Galanin in Alzheimer's disease: neuroinhibitory or neuroprotective? | journal = Cellular and Molecular Life Sciences | volume = 65 | issue = 12 | pages = 1842–1853 | date = June 2008 | pmid = 18500641 | pmc = 2911017 | doi = 10.1007/s00018-008-8159-2 }}</ref> | ||
| <ref name=" |
<ref name="pmid16246567">{{cite journal | vauthors = Ding X, MacTavish D, Kar S, Jhamandas JH | title = Galanin attenuates beta-amyloid (Abeta) toxicity in rat cholinergic basal forebrain neurons | journal = Neurobiology of Disease | volume = 21 | issue = 2 | pages = 413–420 | date = February 2006 | pmid = 16246567 | doi = 10.1016/j.nbd.2005.08.016 | s2cid = 53192040 }}</ref> | ||
| <ref name=" |
<ref name="pmid15350653">{{cite journal | vauthors = Mazarati A, Lu X, Shinmei S, Badie-Mahdavi H, Bartfai T | title = Patterns of seizures, hippocampal injury and neurogenesis in three models of status epilepticus in galanin receptor type 1 (GalR1) knockout mice | journal = Neuroscience | volume = 128 | issue = 2 | pages = 431–441 | year = 2004 | pmid = 15350653 | pmc = 1360211 | doi = 10.1016/j.neuroscience.2004.06.052 }}</ref> | ||
| <ref name="pmid15944034">{{cite journal | vauthors = Berger A, Santic R, Hauser-Kronberger C, Schilling FH, Kogner P, Ratschek M, Gamper A, Jones N, Sperl W, Kofler B | display-authors = 6 | title = Galanin and galanin receptors in human cancers | journal = Neuropeptides | volume = 39 | issue = 3 | pages = 353–359 | date = June 2005 | pmid = 15944034 | doi = 10.1016/j.npep.2004.12.016 | s2cid = 1108702 }}</ref> | |||
| }} | |||
| <ref name="pmid16052044">{{cite journal | vauthors = Lundström L, Elmquist A, Bartfai T, Langel U | title = Galanin and its receptors in neurological disorders | journal = Neuromolecular Medicine | volume = 7 | issue = 1–2 | pages = 157–180 | year = 2005 | pmid = 16052044 | doi = 10.1385/NMM:7:1-2:157 | s2cid = 19729607 }}</ref> | |||
| <ref name="pmid18500643">{{cite journal | vauthors = Mechenthaler I | title = Galanin and the neuroendocrine axes | journal = Cellular and Molecular Life Sciences | volume = 65 | issue = 12 | pages = 1826–1835 | date = June 2008 | pmid = 18500643 | doi = 10.1007/s00018-008-8157-4 | s2cid = 8754964 | pmc = 11131683 }}</ref> | |||
| <ref name="pmid2448788">{{cite journal | vauthors = Kaplan LM, Spindel ER, Isselbacher KJ, Chin WW | title = Tissue-specific expression of the rat galanin gene | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 4 | pages = 1065–1069 | date = February 1988 | pmid = 2448788 | pmc = 279702 | doi = 10.1073/pnas.85.4.1065 | doi-access = free | bibcode = 1988PNAS...85.1065K }}</ref> | |||
| ==Further reading== | |||
| {{Refbegin| 2}} | |||
| {{PBB_Further_reading | |||
| | citations = | |||
| *{{Cite journal | author=Vrontakis ME |title=Galanin: a biologically active peptide. |journal=Current drug targets. CNS and neurological disorders |volume=1 |issue= 6 |pages= 531–41 |year= 2003 |pmid= 12769595 |doi=10.2174/1568007023338914 }} | |||
| *{{Cite journal | author=Mufson EJ, Counts SE, Perez SE, Binder L |title=Galanin plasticity in the cholinergic basal forebrain in Alzheimer's disease and transgenic mice. |journal=Neuropeptides |volume=39 |issue= 3 |pages= 233–7 |year= 2005 |pmid= 15893372 |doi= 10.1016/j.npep.2004.12.005 }} | |||
| *{{Cite journal | author=Robinson JK, Bartfai T, Langel U |title=Galanin/GALP receptors and CNS homeostatic processes. |journal=CNS & neurological disorders drug targets |volume=5 |issue= 3 |pages= 327–34 |year= 2006 |pmid= 16787232 |doi=10.2174/187152706777452281 }} | |||
| *{{Cite journal | author=McKnight GL, Karlsen AE, Kowalyk S, ''et al.'' |title=Sequence of human galanin and its inhibition of glucose-stimulated insulin secretion from RIN cells. |journal=Diabetes |volume=41 |issue= 1 |pages= 82–7 |year= 1992 |pmid= 1370155 |doi=10.2337/diabetes.41.1.82 }} | |||
| *{{Cite journal | author=Gai WP, Geffen LB, Blessing WW |title=Galanin immunoreactive neurons in the human hypothalamus: colocalization with vasopressin-containing neurons. |journal=J. Comp. Neurol. |volume=298 |issue= 3 |pages= 265–80 |year= 1990 |pmid= 1698834 |doi= 10.1002/cne.902980302 }} | |||
| *{{Cite journal | author=Burleigh DE, Furness JB |title=Distribution and actions of galanin and vasoactive intestinal peptide in the human colon. |journal=Neuropeptides |volume=16 |issue= 2 |pages= 77–82 |year= 1991 |pmid= 1701228 |doi=10.1016/0143-4179(90)90115-F }} | |||
| *{{Cite journal | author=Fried G, Meister B, Rådestad A |title=Peptide-containing nerves in the human pregnant uterine cervix: an immunohistochemical study exploring the effect of RU 486 (mifepristone). |journal=Hum. Reprod. |volume=5 |issue= 7 |pages= 870–6 |year= 1991 |pmid= 1702449 |doi= }} | |||
| *{{Cite journal | author=Hyde JF, Engle MG, Maley BE |title=Colocalization of galanin and prolactin within secretory granules of anterior pituitary cells in estrogen-treated Fischer 344 rats. |journal=Endocrinology |volume=129 |issue= 1 |pages= 270–6 |year= 1991 |pmid= 1711463 |doi=10.1210/endo-129-1-270 }} | |||
| *{{Cite journal | author=Bennet WM, Hill SF, Ghatei MA, Bloom SR |title=Galanin in the normal human pituitary and brain and in pituitary adenomas. |journal=J. Endocrinol. |volume=130 |issue= 3 |pages= 463–7 |year= 1991 |pmid= 1719117 |doi=10.1677/joe.0.1300463 }} | |||
| *{{Cite journal | author=Schmidt WE, Kratzin H, Eckart K, ''et al.'' |title=Isolation and primary structure of pituitary human galanin, a 30-residue nonamidated neuropeptide. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue= 24 |pages= 11435–9 |year= 1992 |pmid= 1722333 |doi=10.1073/pnas.88.24.11435 | pmc=53150 }} | |||
| *{{Cite journal | author=Bauer FE, Christofides ND, Hacker GW, ''et al.'' |title=Distribution of galanin immunoreactivity in the genitourinary tract of man and rat. |journal=Peptides |volume=7 |issue= 1 |pages= 5–10 |year= 1986 |pmid= 2423990 |doi=10.1016/0196-9781(86)90052-5 }} | |||
| *{{Cite journal | author=Bauer FE, Adrian TE, Christofides ND, ''et al.'' |title=Distribution and molecular heterogeneity of galanin in human, pig, guinea pig, and rat gastrointestinal tracts. |journal=Gastroenterology |volume=91 |issue= 4 |pages= 877–83 |year= 1986 |pmid= 2427385 |doi= }} | |||
| *{{Cite journal | author=Tainio H, Vaalasti A, Rechardt L |title=The distribution of substance P-, CGRP-, galanin- and ANP-like immunoreactive nerves in human sweat glands. |journal=Histochem. J. |volume=19 |issue= 6-7 |pages= 375–80 |year= 1987 |pmid= 2444569 |doi=10.1007/BF01680455 }} | |||
| *{{Cite journal | author=Maggi CA, Santicioli P, Patacchini R, ''et al.'' |title=Galanin: a potent modulator of excitatory neurotransmission in the human urinary bladder. |journal=Eur. J. Pharmacol. |volume=143 |issue= 1 |pages= 135–7 |year= 1988 |pmid= 2446889 |doi=10.1016/0014-2999(87)90744-8 }} | |||
| *{{Cite journal | author=Marti E, Gibson SJ, Polak JM, ''et al.'' |title=Ontogeny of peptide- and amine-containing neurones in motor, sensory, and autonomic regions of rat and human spinal cord, dorsal root ganglia, and rat skin. |journal=J. Comp. Neurol. |volume=266 |issue= 3 |pages= 332–59 |year= 1988 |pmid= 2447134 |doi= 10.1002/cne.902660304 }} | |||
| *{{Cite journal | author=Beal MF, Clevens RA, Chattha GK, ''et al.'' |title=Galanin-like immunoreactivity is unchanged in Alzheimer's disease and Parkinson's disease dementia cerebral cortex. |journal=J. Neurochem. |volume=51 |issue= 6 |pages= 1935–41 |year= 1988 |pmid= 2460590 |doi=10.1111/j.1471-4159.1988.tb01181.x }} | |||
| *{{Cite journal | author=Berrettini WH, Kaye WH, Sunderland T, ''et al.'' |title=Galanin immunoreactivity in human CSF: studies in eating disorders and Alzheimer's disease. |journal=Neuropsychobiology |volume=19 |issue= 2 |pages= 64–8 |year= 1989 |pmid= 2465504 |doi=10.1159/000118436 }} | |||
| }} | }} | ||
| {{Refend}} | |||
| ==External links== | == External links == | ||
| * {{MeshName|Galanin}} | * {{MeshName|Galanin}} | ||
| {{Neuropeptides}} | {{Neuropeptides}} | ||
| {{Neuropeptidergics}} | |||
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Latest revision as of 19:04, 2 October 2024
| Identifiers | |
|---|---|
| CAS Number | |
| ChemSpider |
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| ChEMBL | |
| Chemical and physical data | |
| Formula | C146H213N43O40 |
| Molar mass | 3210.571 g·mol |
| (what is this?) (verify) | |
Galanin is a neuropeptide encoded by the GAL gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors.
Much of galanin's functional role is still undiscovered. Galanin is closely involved in the modulation and inhibition of action potentials in neurons. Galanin has been implicated in many biologically diverse functions, including: nociception, waking and sleep regulation, cognition, feeding, regulation of mood, regulation of blood pressure, it also has roles in development as well as acting as a trophic factor. Galanin neurons in the medial preoptic area of the hypothalamus may govern parental behaviour. Galanin is linked to a number of diseases including Alzheimer's disease, epilepsy as well as depression, eating disorders, cancer, and addiction. Galanin appears to have neuroprotective activity as its biosynthesis is increased 2-10 fold upon axotomy in the peripheral nervous system as well as when seizure activity occurs in the brain. It may also promote neurogenesis.
Galanin is predominantly an inhibitory, hyperpolarizing neuropeptide and as such inhibits neurotransmitter release. Galanin is often co-localized with classical neurotransmitters such as acetylcholine, serotonin, and norepinephrine, and also with other neuromodulators such as neuropeptide Y, substance P, and vasoactive intestinal peptide.
Discovery
Galanin was first identified from porcine intestinal extracts in 1978 by Professor Viktor Mutt and colleagues at the Karolinska Institute, Sweden using a chemical assay technique that detects peptides according to its C-terminal alanine amide structure. Galanin is so-called because it contains an N-terminal glycine residue and a C-terminal alanine. The structure of galanin was determined in 1983 by the same team, and the cDNA of galanin was cloned from a rat anterior pituitary library in 1987.
Tissue distribution
Galanin is located predominantly in the central nervous system and gastrointestinal tract. Within the central nervous system, highest concentrations are found in the hypothalamus, with lower levels in the cortex and brainstem. In the hypothalamus, it is for example found in the ventrolateral preoptic nucleus where it has sleep-promoting function. Within the brain, galanin has also been found in the ventral forebrain and amygdala. Along with this, the immune reaction of galanin in the brain is centered in the hypothalamopituitary. Gastrointestinal galanin is most abundant in the duodenum, with lower concentrations in the stomach, small intestine, and colon. Galanin is also expressed in the skin where is serves anti-inflammatory functions. Specifically, it has been found in keratinocytes, eccrine sweat glands, and around blood vessels. Galanin has been found in endocrine tumors. Within gastric cancer cells, galanin has been found to have a tumor suppressive role, but hypermethylation has been shown to stop its tumor suppressive properties.
Structure
| Species | 1 | 6 | 11 | 16 | 21 | 26 ! |
|---|---|---|---|---|---|---|
| Pig | G W T L N | S A G Y L | L G P H A | I D N H R | S F H D K | Y G L A * |
| Human | G W T L N | S A G Y L | L G P H A | V G N H R | S F S D K | N G L T S ** |
| Cow | G W T L N | S A G Y L | L G P H A | L D S H R | S F Q D K | H G L A * |
| Rat | G W T L N | S A G Y L | L G P H A | I D N H R | S F S D K | H G L T* |
| * C-terminal amide ** C-terminal free acid | ||||||
Galanin is a peptide consisting of a chain of 29 amino acids (30 amino acids in humans) produced from the cleavage of a 123-amino acid protein known as prepro galanin, which is encoded by the GAL gene. The sequence of this gene is highly conserved among mammals, showing over 85% homology between rat, mouse, porcine, bovine, and human sequences. In these animal forms, the first 15 amino acids from the N-terminus are identical, but amino acids differ at several positions on the C-terminal end of the protein.
These slight differences in protein structure have far-reaching implications on their function. For example, porcine and rat galanin inhibit glucose-induced insulin secretion in rats and dogs but have no effect on insulin secretion in humans. This demonstrates that it is essential to study the effects of galanin and other regulatory peptides in their autologous species.
The galanin family of protein consists of four proteins, of which GAL was the first to be identified. The second was galanin message-associated protein (GMAP), a 59- or 60-amino acid peptide also formed from the cleavage of prepro galanin. The other two peptides, galanin-like peptide (GALP) and alarin, were identified relatively recently and are both encoded for in the same gene, the prepro GALP gene. GALP and alarin are produced by different post-transcriptional splicing of this gene.
Protein family
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Protein family
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Receptors
Galanin signalling occurs through three classes of receptors, GALR1, GALR2, and GALR3, which are all part of the G protein-coupled receptor (GPCR) superfamily. Galanin receptors are expressed in the central nervous system, in the pancreas, and on solid tumours. The level of expression of the different receptors varies at each location, and this distribution changes after injury to neurons. Experiments into the function of the receptor subtypes involve mostly genetic knockout mice. The location of the receptor and the combination of receptors that are inhibited or stimulated heavily affect the outcome of galanin signalling.
Clinical characteristics
Appetite
Injections of galanin into the lateral ventricle or directly into the hypothalamus creates the urge to feed, with a preference for eating fats. Galanin also regulates glucose metabolism and can potentially alleviate symptoms of Diabetes Type II due to its interaction with insulin resistance. Galanin is an inhibitor of pancreatic secretion of insulin.
Addiction
Galanin plays a role in addiction regulation. It is involved in repeated alcohol intake. Along with addiction to alcohol, galanin has been shown to play a role in addiction to nicotine and opiates.
Alzheimer's disease
One of the pathological features of the brain in the later stages of Alzheimer's disease is the presence of overgrown GAL-containing fibres innervating the surviving cholinergic neurons. Another feature is an increase in the expression of GAL and GAL receptors, in which increases of up to 200% have been observed in postmortem brains of Alzheimer's patients. The cause and role of this increase is poorly understood.
It has been suggested that the hyper-innervation acts to promote the death of these neurons and that the inhibitory effect of galanin on cholinergic neurons worsened the degeneration of cognitive function in patients by decreasing the amount of acetylcholine available to these neurons.
A second hypothesis has been generated based on data that suggest GAL is involved in protecting the hippocampus from excitotoxic damage and the neurons in the cholinergic basal forebrain from amyloid toxicity.
Cognitive performance
Galanin participates in cognitive performance and has been shown to weaken learning and cognition.
Depression
Noradrenaline and serotonin, two neurotransmitters involved in depression, are both co-expressed and modulated by galanin, suggesting that galanin plays a role in the regulation of depression. Stimulation of the Gal1 and Gal3 receptors result in depression-like behaviors, whereas stimulation of the Gal2 receptor results in reduced depression-like behaviors. Currently, one of the potential mechanisms for this is that galanin stimulates the hypothalamus-pituitary-adrenal axis, which leads to an increase in glucocorticoid secretion. Increased levels of glucocorticoid hormones is common in those who suffer from depression.
Endocrine
Galanin inhibits the secretion of insulin and somatostatin and stimulates the secretion of glucagon, prolactin, somatotropin, adrenocorticotropin, luteinizing hormone, foliculotropin, growth hormone-releasing hormone, hypothalamic gonadotropin-releasing hormone, and corticotropin-releasing hormone.
Epilepsy
Galanin in the hippocampus is an inhibitor of glutamate but not of GABA. This means that galanin is capable of increasing the seizure threshold and, therefore, is expected to act as an anticonvulsant. To be specific, GalR1 has been linked to the suppression of spontaneous seizures. An agonist antiepileptic drug candidate is NAX 5055.
In development
It has been shown that galanin plays a role in the control of the early post-natal neural development of the dorsal root ganglion (DRG). Galanin-mutant animals show a 13% decrease in the number of adult DRG cells as well as a 24% decrease in the percentage of cells expressing substance P. This suggests that the cell loss by apoptosis that usually occurs in the developing DRG is regulated by galanin and that the absence of galanin results in an increase in the number of cells that die.
Pain and neuroprotection
Galanin plays an inhibitory role in pain processing, with high doses having been shown to reduce pain. When galanin is added to the spinal cord, neuropathic pain is reduced. Along with this, galanin is believed to be effective in reducing spinal hyperexcitability. Sensory neurons increasingly release galanin when they are damaged. An increase in the concentrations of galanin are also believed to be for neuroprotective reasons and lead to promoted neurogenesis. GalR2 activation is believed to mediate the survival role galanin plays in the dorsal root ganglion.
Parental role in mice
Galanin-expressing neurons in the medial preoptic area of the brain are responsible for regulating aggression towards pups by male mice.
Galanin-expressing neurons in the medial preoptic area are remodelled during pregnancy. Estrogen and progesterone genomic receptors in galanin (Gal)-expressing neurons control discrete aspected of plasticity.
See also
References
- ^ GRCh38: Ensembl release 89: ENSG00000069482 – Ensembl, May 2017
- ^ GRCm38: Ensembl release 89: ENSMUSG00000024907 – Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Evans H, Baumgartner M, Shine J, Herzog H (December 1993). "Genomic organization and localization of the gene encoding human preprogalanin". Genomics. 18 (3): 473–477. doi:10.1016/S0888-7543(11)80002-9. PMID 7508413.
- ^ Mitsukawa K, Lu X, Bartfai T (June 2008). "Galanin, galanin receptors and drug targets". Cellular and Molecular Life Sciences. 65 (12): 1796–1805. doi:10.1007/s00018-008-8153-8. PMC 11131746. PMID 18500647. S2CID 263470319.
- Mechenthaler I (June 2008). "Galanin and the neuroendocrine axes". Cellular and Molecular Life Sciences. 65 (12): 1826–1835. doi:10.1007/s00018-008-8157-4. PMC 11131683. PMID 18500643. S2CID 8754964.
- ^ Wu Z, Autry AE, Bergan JF, Watabe-Uchida M, Dulac CG (May 2014). "Galanin neurons in the medial preoptic area govern parental behaviour". Nature. 509 (7500): 325–330. Bibcode:2014Natur.509..325W. doi:10.1038/nature13307. PMC 4105201. PMID 24828191.
- Lundström L, Elmquist A, Bartfai T, Langel U (2005). "Galanin and its receptors in neurological disorders". Neuromolecular Medicine. 7 (1–2): 157–180. doi:10.1385/NMM:7:1-2:157. PMID 16052044. S2CID 19729607.
- Berger A, Santic R, Hauser-Kronberger C, Schilling FH, Kogner P, Ratschek M, et al. (June 2005). "Galanin and galanin receptors in human cancers". Neuropeptides. 39 (3): 353–359. doi:10.1016/j.npep.2004.12.016. PMID 15944034. S2CID 1108702.
- Ito M (September 2009). "Functional roles of neuropeptides in cerebellar circuits". Neuroscience. 162 (3): 666–672. doi:10.1016/j.neuroscience.2009.01.019. PMID 19361475. S2CID 207245197.
- ^ Bartfai T (2000). "Galanin – A neuropeptide with important central nervous system actions". Archived from the original on December 2, 2010. Retrieved November 19, 2009.
- ^ Wynick D, Thompson SW, McMahon SB (February 2001). "The role of galanin as a multi-functional neuropeptide in the nervous system". Current Opinion in Pharmacology. 1 (1): 73–77. doi:10.1016/S1471-4892(01)00006-6. PMID 11712539.
- ^ Hökfelt T, Tatemoto K (June 2008). "Galanin--25 years with a multitalented neuropeptide". Cellular and Molecular Life Sciences. 65 (12): 1793–1795. doi:10.1007/s00018-008-8152-9. PMC 11131681. PMID 18500648. S2CID 19878753.
- ^ Kuteeva E, Hökfelt T, Wardi T, Ogren SO (2010). Hökfelt T (ed.). "Galanin, galanin receptor subtypes and depression-like behaviour". Experientia Supplementum (2012). Experientia Supplementum. 102. Springer: 163–181. doi:10.1007/978-3-0346-0228-0_12. ISBN 978-3-0346-0227-3. PMID 21299068.
- Ch'ng JL, Christofides ND, Anand P, Gibson SJ, Allen YS, Su HC, et al. (October 1985). "Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury". Neuroscience. 16 (2): 343–354. doi:10.1016/0306-4522(85)90007-7. PMID 2417156. S2CID 32774212.
- Kaplan LM, Spindel ER, Isselbacher KJ, Chin WW (February 1988). "Tissue-specific expression of the rat galanin gene". Proceedings of the National Academy of Sciences of the United States of America. 85 (4): 1065–1069. Bibcode:1988PNAS...85.1065K. doi:10.1073/pnas.85.4.1065. PMC 279702. PMID 2448788.
- ^ Bauer JW, Lang R, Jakab M, Kofler B (2010). Hökfelt T (ed.). "Galanin family of peptides in skin function". Experientia Supplementum (2012). Experientia Supplementum. 102. Springer: 51–59. doi:10.1007/978-3-0346-0228-0_5. ISBN 978-3-0346-0227-3. PMID 21299061.
- ^ Mitsukawa K, Lu X, Bartfai T (2010). Hökfelt T (ed.). "Galanin, galanin receptors, and drug targets". Experientia Supplementum (2012). Experientia Supplementum. 102. Springer: 7–23. doi:10.1007/978-3-0346-0228-0_2. ISBN 978-3-0346-0227-3. PMID 21299058.
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External links
- Galanin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
| Peptides: neuropeptides | |||||||||||
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| Hormones | see hormones | ||||||||||
| Opioid peptides |
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| Other neuropeptides |
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