Effects of terpenoids on C. elegans neuromuscular transmission

TURANI, O.; HERNANDO G; BOUZAT, C.

Congreso; 2nd Congress of the Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN); 2016

The free-living nematode Caenorhabditis elegans is a model organism to study the nervous system. Nematode muscle Cys-loop receptors mediate rapid synaptic transmission and are involved in neuromuscular transmission and worm locomotion. In parasites, they are clinically important because they are targets of anthelmintic drugs. We use C. elegans to identify novel anthelmintic agents and the target receptors. We found that three terpenoids, thymol, carvacrol, and eugenol, impair locomotion of wild-type C. elegans. The three compounds (< 2 mM) paralyzeadult and larval worms in less than 2 h, indicating a rapid action compatible with the involvement of ligand-gated ion channels. The type of paralysis induced by all compounds is neither flaccid, as that induced by GABA activation, nor spastic, as that induced by activation of nicotinic receptors (nAChRs). To gain further insights into the potential drug targets we tested their effects on null mutants of Cys-loop receptors involved in locomotion. We found that glutamate receptors are not involved in the effect. In contrast, worms lacking UNC-49 (GABA) receptors or Levamisole-sensitivenAChRs are partially resistant to these compounds. Thus, these two receptors are the targets of the terpenoids. Their dual action explains the observed intermediate phenotypes. The discovery of novel paralyzing compounds and their receptor targets in C. elegans contributes to the development of anthelmintic therapies.