Acetylcholine and GABA responses at the neuromuscular junction of the nematode Caenorhabditis elegans are nagatively modulated by terpenoids

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

Mar del Plata

Congreso; Segunda Reunión Conjunta de Sociedades de BioCiencias.; 2017

SAIC, SAFE, SAB, SAP, SAH, SAA, SAI

Parasitic nematodes infect many species of animals throughout the phyla, including humans. These nematodes place a major burden on human health and livestock production. Many anthelmintic drugs are losing their effectiveness because drug-resistant nematode strains are emerging. There is a need for concerted efforts to incorporate novel drugs. Medicinal plants provide an alternative source of potential anthelmintic compounds, and the free-living nematode Caenorhabditis elegans is a good animal model for drug screening and for the identification of drug actions. The levamisole-sensitive acetylcholine receptor (L-AChR) and the GABA-A receptor are involved in nematode muscle contraction and are targets of widely used anthelmintic drugs. By using plant extracts, we identified three terpenoids -thymol, carvacrol and eugenol- that have the capability to paralyze C. elegans, with a potency order of carvacrol>thymol>eugenol. Behavioral assays in C. elegans strains lacking Cys-loop receptor subunits showed that L-AChR and GABA-A receptor are involved in the terpenoid-induced paralysis. Also, thymol potentiates the paralyzing actions of established anthelmintic agents, indicating that it can be used in combination with these drugs as a strategy to reduce acquisition of resistance. Electrophysiological assays in C. elegans L1 muscle cells revealed that terpenoids are not capable of eliciting macroscopic currents but they significantly reduce AChand GABA-elicited responses. Single-channel activity of L-AChRs in presence of terpenoids is significantly reduced but the channel properties remain constant. These results are compatible with the action of the compounds as antagonists or allosteric inhibitors of muscle Cys-loop receptors. Thus, by acting at the neuromuscular junction, terpenoids are novel anthelmintic candidates. We propose that medicinal plants that contain terpenoids can be an alternativesource of anthelmintic compounds