RH DOMAIN OF GRK2 INCREASES ENDOTHELIN RECEPTOR RESPONSE IN CARDIOMYOCYTES

SONIA RIPOLL; MARTINA IRARRAZABAL; EMILIANA ECHEVERRÍA; CARINA SHAYO; NATALIA FERNANDEZ

Mar del Plata

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2023

SAIC

Endothelin-1 is a potent vasoconstrictor that exerts its effects through two Gq protein-coupled receptors, ETA and ETB. We previously described that ETA desensitization is mediated by GRK2 through two mechanisms: one involving phosphorylation and the other mediated by its RGS-homologous (RH) domain. Considering that ETA desensitization can lead to heterologous desensitization of the insulin receptor and taking into account that arterial hypertension and insulin resistance are comorbidities where GRK2 is up-regulated, we aimed to study the molecular mechanisms linking these three components in isolated rat cardiomyocytes. In isolated hearts of spontaneously hypertensive rats, a model that besides of hypertensive is insulin resistant, we observed by qPCR a 2.7-fold increase (p