Pharmacology of nicotinic receptors from C. elegans muscle

BERGÉ, I.; DIONISIO, L.; BOUZAT, C.

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011

Caenorhabditis elegans has emerged as a model organism useful for drug screening. Itexpresses two types of muscle nicotinic receptors (AChRs): levamisole-sensitive (L-AChR) andnicotine-sensitive (N-AChR). L-AChRs are targets of anthelmintic drugs, which act as specificand potent agonists. We here explore activation of both AChR types by the nematocide drugoxantel. Single-channel recordings from C. elegans muscle cultured cells show that oxantelelicits openings with amplitudes similar to those of L-AChRs. However, the frequency ofopening is significantly reduced with respect to that observed in the presence of ACh,indicating reduced activation. In whole cell recordings from cells expressing N-AChRs, peakcurrents elicited by oxantel are 45% of those elicited by ACh. Molecular docking studies showbinding of oxantel to both types of AChRs, with similar binding energies but differentorientations at the binding pocket. We conclude that oxantel behaves as a partial and nonselective agonist of both L- and N-muscle AChRs, thus showing a different pharmacologicalprofile compared to that of typical anthelmintic agents. These results contribute to theunderstanding of the pharmacology related to neuromuscular transmission in the modelorganism.