Estudo da modulação da função cardíaca pelos receptores purinérgicos em átrios de ratos Wistar - EPM-1

• Grant number: 12/24828-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2013
• End date: November 30, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Aron Jurkiewicz
• Grantee: Henrique Camara
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Purine, like ATP, and pyrimidine, as UTP are stored with norepinephrine in synaptic vesicles and are released by sympathetic neurons. The action of these nucleotides in these synapses is mediated by P1 and P2 purinergic receptors, which are expressed in cardiac tissues. Studies show the role of the purinergic system in the regulation of cardiac function. Both nucleotides stimulate vasoconstriction and vasodilatation, vascular muscle and endothelial cell growth, angiogenesis, and vascular remodeling. Furthermore, purinoceptors modulate cardiac inotropic and chronotropic. Since the role of cellular and molecular mechanisms of purinoceptors in the heart needs more studies, especially involving chronotropic effects, it became important to investigate the role of these receptors in the regulation of atrial function in Wistar rats. We are going to isolate the right atria (RA) and left atria (LA) of normotensive Wistar rats (NWR) from 4 to 6 months old, performing a functional study to investigate the cellular mechanisms involved in the activation of P1 and P2 purinergic receptors on the modulation of chronotropism in RA. We are going to use selective agonists and antagonists for purinergic receptors P1, focusing on its four subtypes A1, A2A, A2B, and A3. The apparent affinity parameter (pD2) will indicate the affinity of the receptor for the P1 receptor agonist. The value of Emax presents how much the signaling pathway of these receptors was activated. The dislocation of the agonist curves by the antagonist will determine pA2, a parameter for studying the pharmacological properties and classifying receptors. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RODRIGUES, JULIANO Q. D.; CAMARA, HENRIQUE; JURKIEWICZ, ARON; GODINHO, ROSELY O.. Increased Gi protein signaling potentiates the negative chronotropic effect of adenosine in the SHR right atrium. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. 391, n. 5, p. 513-522, MAY 2018. (13/20402-6, 12/22763-3, 15/07019-4, 12/24828-5)

DANTAS RODRIGUES, JULIANO QUINTELLA; CAMARA, HENRIQUE; DA SILVA JUNIOR, EDILSON DANTAS; GODINHO, ROSELY OLIVEIRA; JURKIEWICZ, ARON. Intrinsic Adaptation of SHR Right Atrium Reduces Heart Rate. Journal of Cardiovascular Pharmacology, v. 74, n. 6, p. 542-548, DEC 2019. (12/22763-3, 15/07019-4, 12/24828-5)