Molecular characterization of a new serotonergic G-protein coupled receptor from cestodes: new potential target for drugs against neglected tropical diseases

CAMICIA, F.; BIVONA, AUGUSTO ERNESTO; URIEL KOZIOL; ROSENZVIT, M.C.; PARK, SANG KYU; PREZA, M; MARCHANT, JONATHAN S.; VACA, HUGO; NAIDICH, A.; CELENTANO, ANA M.

Buenos Aires

Congreso; Reunión Conjunta SAIC SAI SAFIS 2020; 2020

Sociedad Argentina de investigacion clinica (SAIC)

Introduction: Echinococcus canadensis is a platyhelminth parasite that belongs to the class Cestoda and is the etiological agent of Hydatid disease, a neglected disease that affects public health and economy in Argentina and worldwide. Currently, the treatment for echinococcosis in humans relies on benzimidazoles. However, the emergence of resistant parasites, makes the discovery of new anthelmintic drugs an imperative need. To tackle this problem, we propose to characterize G-protein coupled receptors from cestodes as new pharmacologicaltargets. In our previous work1, we found that serotonergic GPCRs (5-HT GPCRs) are of major importance in cestode movement and showed distinctive pharmacology. Objective: the aim of this work was the bioinformatical characterization, function and localization of a new 5-HT GPCR from Echinococcus canadensis. Material and methods: Bioinformatics analyses suggest the existence of genes encoding 5-HT GPCRs. Using this information, a novel cDNA coding for a new 5-HT GPCR was cloned, sequenced and expressed in HEK293 cells. Intracellular levels of calcium were measured. Hyperimmune antiserum was generated against the receptor protein and confocal laser microscopy was used to study the localization of the receptor. Results: When the cell line was transfected with a gene encoding for the receptor, the calcium levels increased only in the presence of serotonin but not with of other biogenic amines. Whole mount immunofluorescence revealed branched fibers corresponding to the nervous system of the worm. Conclusion: The dataset confirms the bioinformatic analyses showing that the cloned gene codes for a new 5-HT GPCR conserved in cestodes with major roles in the nervous system of the parasite. The molecule analyzed here could be exploited at the pharmacological level to design or repurpose drugs to treat neglected diseases caused by cestode parasites.References 1. Camicia F et al. PLoS Negl Trop Dis. 2018 Feb 9;12(2):e0006267.