Neurochemistry and Neuropharmacology
Author: Ornella Turani | email: ornellaturani@gmail.com
Ornella Turani 1°, Guillermina Hernando 1°, Cecilia Bouzat 1°
1° Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB)
The free-living nematode Caenorhabditis elegans is a model of parasitic nematodes. It has a great variety of nicotinic receptors (nAChR), some of which may be novel antiparasitic drug targets. Because resistance of parasitic nematodes to the limited number of anthelmintic drugs available has become an important problem in human and veterinary health, elucidation of the functional roles and drug selectivity of their targets is of great importance for the development of novel drugs. ACR-23 is a nAChR subtype present in neuronal and muscle cells of nematodes but not in vertebrates. It is a cation-selective channel activated by betaine (BE) and sensitive to monepantel (MNP), one of the newest anthelmintic drugs. By performing locomotion assays of wild-type adult worms we showed that exogenous BE significantly increased motility. This effect was not observed in acr-23 mutants, indicating that the enhancement of ACR-23 activity causes worm hypermotility. The exposure of worms to MNP produced the opposite effect, resulting in reduced motility. It also induced spastic paralysis and inhibited egg hatching, indicating important anthelmintic ability. By using a primary culture of C. elegans muscle cells, we described for the first time the properties of BE-elicited single-channel currents and their modulation by MNP. Our study provides insights into the molecular basis of anthelmintic action, which pave the way for the development of novel drugs.