Isopimaric acid

Isopimaric acid

Names
IUPAC name (1R,4aR,4bS,7R,10aR)-7-Ethenyl-1,4a,7-trimethyl-3,4,4b,5,6,9,10, 10a-octahydro-2H-phenanthrene-1-carboxylic acid
Identifiers
CAS Number	5835-26-7
ChEBI	CHEBI:6039
ChEMBL	ChEMBL512164
ChemSpider	390596
Jmol interactive 3D	Image
KEGG	C09118
PubChem	442048
InChI InChI=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 Key: MXYATHGRPJZBNA-KRFUXDQASA-N 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 Key: MXYATHGRPJZBNA-KRFUXDQABR
SMILES [H][C@]12[C@](C)(C(O)=O)CCC[C@]1(C)[C@]3([H])C(C[C@](C=C)(C)CC3)=CC2
Properties
Chemical formula	C20H30O2
Molar mass	302.46 g·mol^−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Isopimaric acid (IPA) is a toxin which acts as a large conductance Ca²⁺-activated K⁺ channel (BK channel) opener.

Sources

IPA originates from many sorts of trees, especially conifers.^[1]

Chemistry

IPA is one of the members of the resin acid group which is a tricyclic diterpene.^[1] It has a condensed three-ring structure, one carboxyl-group and a (conjugated) double bond.^[2]

Target

IPA acts on the large-conductance calcium activated K+ channels (BK channels).^[3][4]

Mode of action

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 Ca²⁺ 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 charybdotoxin (CTX).^[3][4] Opening of the BK channel leads to an increased K⁺-efflux which hyperpolarizes the resting membrane potential, reducing the excitability of the cell in which the BK-channel is expressed.

Toxicity

Studies on rainbow trout hepatocytes have shown that IPA increases intracellular calcium release, leading to a disturbance in the calcium homeostasis. This could be important in the possible toxicity of the toxin.

Therapeutic use

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.^[4]

Notes

1. Wilson, AE; Moore, ER; Mohn, WW (1996). "Isolation and characterization of isopimaric acid-degrading bacteria from a sequencing batch reactor". Applied and Environmental Microbiology 62 (9): 3146–51. PMC 168108. PMID 8795202.
2. Hwang, J. S. (1996). Modern solder technology for competitive electronics manufacturing. Electronic packaging and interconnection series McGraw-Hill
3. Kaczorowski, GJ; Knaus, HG; Leonard, RJ; McManus, OB; Garcia, ML (1996). "High-conductance calcium-activated potassium channels; structure, pharmacology, and function". Journal of bioenergetics and biomembranes 28 (3): 255–67. doi:10.1007/bf02110699. PMID 8807400.
4. Imaizumi, Y; Sakamoto, 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): 836–46. doi:10.1124/mol.62.4.836. PMID 12237330.

References

• Råbergh, Christina M.I.; Lilius, Henrik; Eriksson, John E.; Isomaa, Boris (1999). "The resin acids dehydroabietic acid and isopimaric acid release calcium from intracellular stores in rainbow trout hepatocytes". Aquatic Toxicology 46: 55–65. doi:10.1016/S0166-445X(98)00115-5.
• Råbergh, 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 hepatocvtes from rainbow trout (Oncorhynchus mykiss)". Aquatic Toxicology 23 (3–4): 169–179. doi:10.1016/0166-445X(92)90050-W.