Marine alkaloids (-)-pictamine and (-)-lepadin B block neuronal nicotinic acetylcholine receptors.

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 (alpha4beta2 and alpha7) expressed in Xenopus oocytes. We found that these alkaloids are potent blockers at these receptors: acetylcholine-elicited currents through alpha4beta2 and alpha7 receptors were blocked by (-)-pictamine with IC(50) values of 1.5 microM and 1.3 microM, respectively, and by (-)-lepadin B with IC(50) values of 0.9 microM and 0.7 microM, respectively. Interestingly, no recovery was observed after the removal of (-)-pictamine in oocytes expressing alpha4beta2 receptors, whereas the inhibited alpha7 currents quickly recovered after the removal of (-)-pictamine. Since there are few compounds that elicit irreversible blocks of alpha4beta2 receptors, (-)-pictamine will be a novel, valuable tool to remove the alpha4beta2-nAChR action from neuronal activities mediated by these two major types of nAChRs.