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标题：Marine Alkaloids (−)-Pictamine and (−)-Lepadin B Block Neuronal Nicotinic Acetylcholine Receptors
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作者：Hiroshi Tsuneki ; Yueren You ; Naoki Toyooka 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2005
卷号：28
期号：4
页码：611-614
DOI：10.1248/bpb.28.611
出版社：The Pharmaceutical Society of Japan
摘要：Ascidians (sea squirts) contain a wealth of alkaloids, but their influence over neuronal nicotinic acetylcholine receptors (nAChRs) has not been evaluated. In this study, we examined the effects of two synthetic compounds, (−)-pictamine, a quinolizidine alkaloid from Clavelina picta , and (−)-lepadin B, a decahydroquinoline alkaloid from Clavelina lepadiformis , on major types of neuronal nicotinic receptors (α4β2 and α7) expressed in Xenopus oocytes. We found that these alkaloids are potent blockers at these receptors: acetylcholine-elicited currents through α4β2 and α7 receptors were blocked by (−)-pictamine with IC₅₀ values of 1.5 μ M and 1.3 μ M , respectively, and by (−)-lepadin B with IC₅₀ values of 0.9 μ M and 0.7 μ M , respectively. Interestingly, no recovery was observed after the removal of (−)-pictamine in oocytes expressing α4β2 receptors, whereas the inhibited α7 currents quickly recovered after the removal of (−)-pictamine. Since there are few compounds that elicit irreversible blocks of α4β2 receptors, (−)-pictamine will be a novel, valuable tool to remove the α4β2-nAChR action from neuronal activities mediated by these two major types of nAChRs.
关键词：nicotinic receptor;ascidians alkaloid;pictamine;Xenopus oocyte