Spirolides and gymnodimine target human muscarinic acetylcholine receptors

Spirolides are a group of cyclic imine marine toxins recently described. Although no human intoxication has been related to their presence in shellfish yet , the possible toxicological consequences to human health are actually unknown. In this work the effects of the 13-desmethyl and 13,19-didesmetyl C spirolides on the activity and the expression of muscarinic acetylcholine receptors (mAChR) were analyzed using a human neuroblastoma cell model. Both spirolides inhibited the acetylcholine-induced calcium signal with a reduction of the maximum response to acetylcholine in the presence of the toxin. The effect of the spirolides persisted after toxin removal suggesting a mAChR irreversible antagonism.