The role of serotonergic G-protein coupled receptors (GPCRs) in Echinococcus granulosus and other cestodes suggests future applications as drug targets of neglected diseases

CAMICIA, FEDERICO; ANA MARÍA CELENTANO; NICOLÁS DI SIERVI; HUGO VACA; LUCAS L MALDONADO; LAURA KAMENETZKY; MARA CECILIA ROSENZVIT

Montevideo

Congreso; Congreso; Expanding Caenorhabditis elegans research: first Latin American worm meeting; 2017; 2017

Introduction:Cestode parasites are a diverse group of organisms, many of them are cause of neglected zoonoses with major impact in health and economy. The adecuate nerve-muscle function is a classical target for cestocide drugs. Genomic and transcriptomic data of E. granulosus (Tsai et al., 2013) and experimental results showing the motor response to serotonin (5-HT) of the larval stage (Camicia et al., 2013) suggest the existence of serotonergic GPCRs (5-HT GPCRs) in this parasite. Drugs that could discriminate between parasite and human GPCRs receptors were not discovered yet.Hypothesis:We propose the existence of 5-HT GPCRs with a major role in parasite movement. Results: The bioinformatics search of this kind of receptors in cestode parasites such as Mesocestoides corti, Echinococcus spp. resulted in the interesting finding of conserved sequences with identity to 5-HT GPCRs, some of them were already cloned and sequenced. The addition of 5-HT to the larval stages of M. corti and E. granulosus resulted in the stimulation of the motility, where as the addition of 5-HT GPCRs antagonists resulted in the inhibition of movement, supporting the importance of 5-HT GPCRs in the parasite movement. Conclusion:The neuromuscular activity in the presence of serotonergic agonists-antagonists suggest the existence of 5-HT GPCRs in cestode parasites. The identification of new GPCRs will be of great impact for the development of new cestocide drugs that could target them.