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

ANA MARÍA CELENTANO; LUCAS MALDONADO; CARLOS DAVIO; NICOLÁS DI SIERVI; SERGIO H. SIMONETTA; MARA C. ROSENZVIT; FEDERICO CAMICIA; HUGO VACA; LAURA KAMENETZKY

Mar del Plata, Provincia de Buenos Aires

Congreso; Reunion Cientifica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio

Introduction: Cestode parasites are a diverse group of organisms, many of them are cause of neglected zoonoses with major impact in local health and global economy. The adecuate nerve-muscle function is essential for the parasitic way of life and is a 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 in this parasite. Drugs that modulate human GPCRs have numerous examples in the pharmaceutical industry but drugs that could discriminate between parasite and human receptors were not discovered yet.Hypothesis: we propose the existence of serotonergic GPCRs with a major role in parasite movement. Results: The bioinformatics search of this kind of receptors in cestode parasites such as Mesocestoides corti, Taenia solium, E. granulosus and Echinococcus multilocularis resulted in the interesting finding of conserved sequences with amino acid identity with serotonergic GPCRs, some of them were already cloned and sequenced. The addition of 5-HT to the larval stages of M. corti and Taenia crassiceps resulted in the stimulation of the motility and significant increases in the endogenous levels of AMPc. Moreover, the strong inhibitory effect of gramine and sumatriptan (two known GPCRs antagonists in mammals) in the stimulatory effects of serotonin is another line of evidence supporting the importance of serotonergic GPCRs in the parasite movement. Conclusion: The cloning and sequencing, neuromuscular activity in the presence of serotonergic agonists-antagonists and the cyclic AMP variations in the presence of serotonin suggest the existence of GPCR for serotonin in E. granulosus and other cestode parasites. The identification of new GPCRs will be of great impact for the development of new cestocide drugs that could target them.