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Ginkgolide B and bilobalide block the pore of the 5-HT?receptor at a location that overlaps the picrotoxin binding site.

ABSTRACT: Extracts from the Ginkgo biloba tree are widely used as herbal medicines, and include bilobalide (BB) and ginkgolides A and B (GA and GB). Here we examine their effects on human 5-HT(3)A and 5-HT(3)AB receptors, and compare these to the effects of the structurally related compounds picrotin (PTN) and picrotoxinin (PXN), the two components of picrotoxin (PTX), a known channel blocker of 5-HT(3), nACh and GABA(A) receptors. The compounds inhibited 5-HT-induced responses of 5-HT(3) receptors expressed in Xenopus oocytes, with IC(50) values of 470 ?M (BB), 730 ?M (GB), 470 ?M (PTN), 11 ?M (PXN) and >1mM (GA) in 5-HT(3)A receptors, and 3.1mM (BB), 3.9 mM (GB), 2.7 mM (PTN), 62 ?M (PXN) and >1mM (GA) in 5-HT(3)AB receptors. Radioligand binding on receptors expressed in HEK 293 cells showed none of the compounds displaced the specific 5-HT(3) receptor antagonist [(3)H]granisetron, confirming that they do not act at the agonist binding site. Inhibition by GB at 5-HT(3)A receptors is weakly use-dependent, and recovery is activity dependent, indicating channel block. To further probe their site of action at 5-HT(3)A receptors, BB and GB were applied alone or in combination with PXN, and the results fitted to a mathematical model; the data revealed partially overlapping sites of action. We conclude that BB and GB block the channel of the 5-HT(3)A receptor. Thus these compounds have comparable, although less potent, behaviour than at some other Cys-loop receptors, demonstrating their actions are conserved across the family.

SUBMITTER: Thompson AJ

PROVIDER: S-EPMC3070799 | biostudies-literature | 2011 Feb-Mar

REPOSITORIES: biostudies-literature

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Ginkgolide B and bilobalide block the pore of the 5-HT₃receptor at a location that overlaps the picrotoxin binding site.

Thompson Andrew J AJ Jarvis Gavin E GE Duke Rujee K RK Johnston Graham A R GA Lummis Sarah C R SC

Neuropharmacology 20101105 2-3

Extracts from the Ginkgo biloba tree are widely used as herbal medicines, and include bilobalide (BB) and ginkgolides A and B (GA and GB). Here we examine their effects on human 5-HT(3)A and 5-HT(3)AB receptors, and compare these to the effects of the structurally related compounds picrotin (PTN) and picrotoxinin (PXN), the two components of picrotoxin (PTX), a known channel blocker of 5-HT(3), nACh and GABA(A) receptors. The compounds inhibited 5-HT-induced responses of 5-HT(3) receptors expres ...[more]

PMID: 21059362

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Dataset Information

Ginkgolide B and bilobalide block the pore of the 5-HT?receptor at a location that overlaps the picrotoxin binding site.

Publications

Ginkgolide B and bilobalide block the pore of the 5-HT₃receptor at a location that overlaps the picrotoxin binding site.

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