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Biochemical and pharmacological characterization of oxytocin forms in New World monkeys: activities on oxytocin and vasopressin receptors

Grant number: 19/09901-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2019
Effective date (End): September 30, 2021
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Rita de Cassia Aleixo Tostes Passaglia
Grantee:Pedro Vargas Pinilla
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:12/20148-0 - Development of new ligands/drugs with selective agonism action (biased agonism) for receptors of the renin-angiotensin and kallikrein-kinin systems: new properties and new biotechnological applications, AP.TEM

Abstract

Oxytocin (OXT) and vasopressin (AVP) are neuropeptides, and their interaction with their receptors (OXTR, AVPR1a, AVPR1b and AVPR2) promotes physiological and behavioral functions. These receptors are part of the large family of G protein-coupled receptors (GPCRs); currently they are target about 40% of all drugs and medications on the market.Although oxytocin is very conserved in placental mammals, our group recently described new variants (Vargas-Pinilla et al., 2015; Parreiras-e-Silva, Vargas-Pinilla, et al. 2017), in New World primates. In our article from 2017 (Parreiras-e-Silva et al., 2017), the variants Pro8OXT e Val3Pro8OXT showed a high efficacy and potency in activation of Gq protein, and at the same time, a low efficacy and potency towards ²-arrestin recruitment, resulting in a lower OXTR internalization and the regulation of the entire OXT-AVP system, producing significant physiological and behavioral effects.In order to advance in this study and to better understanding of functionally OXT variants, we aim to expand the biochemical and pharmacological characterization of new OXT variants through activating the human and cognate receptors from New World primates. To reach such goals, we will use assays based on the Bioluminescence Resonance Energy Transfer (BRET) technology for the G protein and ²-arrestin signaling profiles. These assays will allow signaling profile characterization of OXT variants in different GPCRs. This information will be important both for the understanding of the evolutionary process that occurs within the New World primates for the emergence of paternal care, as well as for use in the design and development of new drugs for the treatment of neuropsychiatric disorders, where the role of the OXT/AVP system is well related.