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Latest revision as of 19:44, 22 December 2024 edit undoCitation bot (talk | contribs)Bots5,429,604 edits Add: bibcode, issue. | Use this bot. Report bugs. | Suggested by Whoop whoop pull up | Category:Potassium channel openers | #UCB_Category 4/13 |
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{{Chembox |
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| verifiedrevid = 328226697 |
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| ImageFile = Cryptopimaric acid.svg |
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| verifiedrevid = 428765989 |
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| ImageFile = Isopimaric acid.svg |
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| IUPACName = |
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| ImageSize = 200px |
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| OtherNames = sandaracopimaric acid |
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| IUPACName = (13''S'')-Pimara-7,15-dien-18-oic acid |
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| Section1 = {{Chembox Identifiers |
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| SystematicName = (1''R'',4a''R'',4b''S'',7''S'',10a''R'')-7-Ethenyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-1-carboxylic acid |
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| CASNo = 471-74-9 |
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| OtherNames = |
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| PubChem = 221580 |
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|Section1={{Chembox Identifiers |
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| CASNo = 5835-26-7 |
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| Section2 = {{Chembox Properties |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| Formula = C<sub>20</sub>H<sub>30</sub>O<sub>2</sub> |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| MolarMass = 302.45 g/mol |
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| UNII = 1E37K85HHK |
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| PubChem = 442048 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 512164 |
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| SMILES = 12(C)(C(O)=O)CCC1(C)3()C(C(C=C)(C)CC3)=CC2 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 390596 |
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| InChI = 1/C20H30O2/c1-5-18(2)12-9-15-14(13-18)7-8-16-19(15,3)10-6-11-20(16,4)17(21)22/h5,7,15-16H,1,6,8-13H2,2-4H3,(H,21,22)/t15-,16+,18-,19+,20+/m0/s1 |
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| InChIKey = MXYATHGRPJZBNA-KRFUXDQABR |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C20H30O2/c1-5-18(2)12-9-15-14(13-18)7-8-16-19(15,3)10-6-11-20(16,4)17(21)22/h5,7,15-16H,1,6,8-13H2,2-4H3,(H,21,22)/t15-,16+,18-,19+,20+/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = MXYATHGRPJZBNA-KRFUXDQASA-N |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 6039 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = C09118}} |
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|Section2={{Chembox Properties |
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| C=20 | H=30 | O=2 |
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'''Isopimaric acid''' (IPA) is a ] which acts as a large conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channel (]) opener. |
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'''Isopimaric acid''' (IPA) is a ] which acts as a large conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channel (]) opener. |
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==Source== |
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==Sources== |
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IPA originates from many sorts of trees, especially conifers.<ref name=Wilson>{{cite journal | pmid = 8795202 | year = 1996 | last1 = Wilson | first1 = AE | last2 = Moore | first2 = ER | last3 = Mohn | first3 = WW | title = Isolation and characterization of isopimaric acid-degrading bacteria from a sequencing batch reactor | volume = 62 | issue = 9 | pages = 3146–51 | pmc = 168108 | journal = Applied and Environmental Microbiology| doi = 10.1128/aem.62.9.3146-3151.1996 | bibcode = 1996ApEnM..62.3146W }}</ref> |
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IPA originates from many sorts of trees, especially conifers (Wilson et al. 1996). |
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==Chemistry== |
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==Chemistry== |
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IPA is one of the members of the ] group which is a tricyclic diterpene (Wilson et al. 1996). It has a condensed three-ring structure, one carboxyl-group and a (conjugated) double bond (Hwang, 1996). |
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IPA is one of the members of the ] group and it is a tricyclic diterpene.<ref name=Wilson/> |
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==Target== |
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==Target== |
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IPA acts on the large-conductance calcium activated K+ channels (]s).<ref name=Kaczorowski>{{cite journal | pmid = 8807400 | year = 1996 | last1 = Kaczorowski | first1 = GJ | last2 = Knaus | first2 = HG | last3 = Leonard | first3 = RJ | last4 = McManus | first4 = OB | last5 = Garcia | first5 = ML | title = High-conductance calcium-activated potassium channels; structure, pharmacology, and function | volume = 28 | issue = 3 | pages = 255–67 | journal = Journal of Bioenergetics and Biomembranes | doi=10.1007/bf02110699| s2cid = 25857254 }}</ref><ref name=Imaizumi>{{cite journal | pmid = 12237330 | year = 2002 | last1 = Imaizumi | first1 = Y | last2 = Sakamoto | first2 = K | last3 = Yamada | first3 = A | last4 = Hotta | first4 = A | last5 = Ohya | first5 = S | last6 = Muraki | first6 = K | last7 = Uchiyama | first7 = M | last8 = Ohwada | first8 = T | title = Molecular basis of pimarane compounds as novel activators of large-conductance Ca(2+)-activated K(+) channel alpha-subunit | volume = 62 | issue = 4 | pages = 836–46 | journal = Molecular Pharmacology | doi=10.1124/mol.62.4.836}}</ref> |
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IPA acts on the large-conductance calcium activated K+ channels (]) (Kaczorowski et al. 1996, Imaizumi et al. 2002). |
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==Mode of action== |
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==Mode of action== |
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BK channels are formed by α subunits and accessory β subunits arranged in tetramers. The α subunit forms the ion conduction pore and the β subunit contributes to channel gating. IPA interaction with the BK channel enhances Ca<sup>2+</sup> and / or voltage sensitivity of the α subunit of BK channels without affecting the channel conductance. In this state BK channels can still be inhibited by one of their inhibitors, like ] (CTX)(Kaczorowski et al. 1996, Imaizumi et al. 2002). Opening of the BK channel leads to an increased K<sup>+</sup>-efflux which hyperpolarizes the ], reducing the excitability of the cell in which the BK-channel is expressed. |
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BK channels are formed by α subunits and accessory β subunits arranged in tetramers. The α subunit forms the ion conduction pore and the β subunit contributes to channel gating. IPA interaction with the BK channel enhances Ca<sup>2+</sup> and / or voltage sensitivity of the α subunit of BK channels without affecting the channel conductance. In this state BK channels can still be inhibited by one of their inhibitors, like ] (CTX).<ref name=Kaczorowski/><ref name=Imaizumi/> Opening of the BK channel leads to an increased K<sup>+</sup>-efflux which hyperpolarizes the ], reducing the excitability of the cell in which the BK-channel is expressed. |
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==Toxicity== |
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==Toxicity== |
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Studies on rainbow ] hepatocytes have shown that IPA increases intracellular ] release, leading to a disturbance in the calcium homeostasis. This could be important in the possible toxicity of the toxin. |
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Studies on rainbow ] hepatocytes have shown that IPA increases intracellular ] release, leading to a disturbance in the calcium homeostasis. This could be important in the possible toxicity of the toxin. |
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==Therapeutic use== |
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==See also== |
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* ] |
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==Notes== |
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This toxin may be of value in the treatment of urinary bladder overactivity, stroke treatment and in problems with the hyperactivity of (vascular) smooth muscle cells (Imaizumi et al. 2002). |
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{{reflist}} |
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==References== |
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==References== |
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* {{cite journal | doi = 10.1016/S0166-445X(98)00115-5 | title = The resin acids dehydroabietic acid and isopimaric acid release calcium from intracellular stores in rainbow trout hepatocytes | year = 1999 | last1 = Råbergh | first1 = Christina M.I. | last2 = Lilius | first2 = Henrik | last3 = Eriksson | first3 = John E. | last4 = Isomaa | first4 = Boris | journal = Aquatic Toxicology | volume = 46 | issue = 1 | pages = 55–65| bibcode = 1999AqTox..46...55R }} |
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<references/> |
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* {{cite journal | doi = 10.1016/0166-445X(92)90050-W | title = The resin acids dehydroabietic acid and isopimaric acid inhibit bile acid uptake and perturb potassium transport in isolated hepatocvtes from rainbow trout (Oncorhynchus mykiss) | year = 1992 | last1 = Råbergh | first1 = C.M.I. | last2 = Isomaa | first2 = B. | last3 = Eriksson | first3 = J.E. | journal = Aquatic Toxicology | volume = 23 | issue = 3–4 | pages = 169–179| bibcode = 1992AqTox..23..169R }} |
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* Imaizumi Y, S. K., Yamada A, Hotta A, Ohya S, Muraki K, Uchiyama M, Ohwada T (2002). "Molecular basis of pimarane compounds as novel activators of large-conductance Ca(2+)-activated K(+) channel alpha-subunit." Molecular Pharmacology 62(4): 836-846 PMID 12237330 |
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* C. M. J. Råbergh, H. L., J. E. Eriksson and B. Isomaa (1999). "The resin acids dehydroabietic acid and isopimaric acid release calcium from intracellular stores in rainbow trout hepatocytes." Aquatic Toxicology 46(1): 55-65 |
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{{Toxins}} |
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* Hwang, J. S. (1996). Modern solder technology for competitive electronics manufacturing Electronic packaging and interconnection series McGraw-Hill |
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{{Ion channel modulators}} |
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* Kaczorowski GJ, K. H., Leonard RJ, McManus OB, Garcia ML (1996). "High-conductance calcium-activated potassium channels; structure, pharmacology, and function." Bioenergenetics and biomembranes 28(3): 255-267 PMID 8807400 |
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* Rabergh, C. M. I., Isomaa, B., Eriksson, J.E. (1992). "The resin acids dehydroabietic acid and isopimaric acid inhibit bile acid uptake and perturb potassium transport in isolated hepatocytes from rainbow trout (Oncorhynchus mykiss)." Aquatic Toxicology 23(3): 169-180 DOI: 10.1016/0166-445X(92)90050-W |
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* Wilson AE, M. E., Mohn WW (1996). "Isolation and characterization of isopimaric acid-degrading bacteria from a sequencing batch reactor." Applied and Environmental Microbiology 62(9): 3146-3151 PMID 8795202 |
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{{Toxins}} |
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