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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Catharanthine alkaloids are noncompetitive antagonists of muscle-type nicotinic acetylcholine receptors.
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Catharanthine alkaloids are noncompetitive antagonists of muscle-type nicotinic acetylcholine receptors.

机译：Catharanine生物碱是肌肉型烟碱乙酰胆碱受体的非竞争性拮抗剂。

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摘要

We compared the interaction of several catharanthine alkaloids including, ibogaine, vincristine, and vinblastine, with that for the noncompetitive antagonist phencyclidine (PCP) at muscle nicotinic acetylcholine receptors (AChRs) in different conformational states. The results established that catharanthine alkaloids: (a) inhibit, in a noncompetitive manner, (+/-)-epibatidine-induced Ca(2+) influx in TE671-halpha1beta1gammadelta cells with similar potencies (IC(50)=17-25microM), (b) inhibit [(3)H]TCP binding to the desensitized Torpedo AChR with higher affinity compared to the resting AChR, and (c) enhance [(3)H]cytisine binding to resting but activatable Torpedo AChRs, suggesting desensitizing properties. Interestingly, PCP inhibits [(3)H]ibogaine binding to the AChR in a steric fashion. This is corroborated by additional docking experiments indicating that the amino groups of neutral ibogaine form hydrogen bonds with the serine ring (position 6'), a location shared with PCP. Since protonated ibogaine forms a salt bridge with one of the acidic residues at the outer ring (position 20'), this ligand could be first attracted to the entrance of the channel by electrostatic interactions. Our data indicate that the catharanthine moiety is a minimum structural requirement for AChR inhibition including, ion channel blocking and desensitization, and that ibogaine and PCP bind to overlapping sites in the desensitized AChR ion channel.
机译：我们比较了几种长春碱生物碱的相互作用，包括依博加因，长春新碱和长春花碱，与非竞争性拮抗剂苯环利定（PCP）在不同构象状态下的肌肉烟碱乙酰胆碱受体（AChRs）的相互作用。结果确定，catharanthine生物碱：（a）以非竞争性方式抑制（+/-）-依巴替丁诱导的TE671-halpha1beta1γδ细胞中的Ca（2+）内流，具有相似的效力（IC（50）= 17-25microM） ，（b）以比静息AChR更高的亲和力抑制[（3）H] TCP与脱敏鱼雷AChR的结合，（c）增强[（3）H]胱氨酸与静息但可激活的鱼雷AChRs的结合，表明脱敏特性。有趣的是，PCP以空间方式抑制[（3）H] ibogaine与AChR的结合。额外的对接实验证实了这一点，该对接实验表明中性伊博加因的氨基与丝氨酸环（位置6'）（与PCP共享的位置）形成氢键。由于质子化的伊博加因与外环（位置20'处）的一个酸性残基形成一个盐桥，因此该配体可首先通过静电相互作用吸引到通道的入口。我们的数据表明，catharanthine部分是抑制AChR的最低结构要求，其中包括离子通道阻断和脱敏作用，并且伊博加因和PCP结合到脱敏AChR离子通道中的重叠位点。

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