Role of Cardiac A2A Receptors Under Normal and Pathophysiological Conditions.

P Boknik,B Hofmann,U Gergs,J Neumann,J Eskandar,N Zimmermann

doi:10.3389/fphar.2020.627838

Abstract

This review presents an overview of cardiac A2A-adenosine receptors The localization of A2A-AR in the various cell types that encompass the heart and the role they play in force regulation in various mammalian species are depicted. The putative signal transduction systems of A2A-AR in cells in the living heart, as well as the known interactions of A2A-AR with membrane-bound receptors, will be addressed. The possible role that the receptors play in some relevant cardiac pathologies, such as persistent or transient ischemia, hypoxia, sepsis, hypertension, cardiac hypertrophy, and arrhythmias, will be reviewed. Moreover, the cardiac utility of A2A-AR as therapeutic targets for agonistic and antagonistic drugs will be discussed. Gaps in our knowledge about the cardiac function of A2A-AR and future research needs will be identified and formulated.

Highlights

There have been many reviews on adenosine receptors (AR), A2A-AR (Fredholm et al, 2001; Haskó and Pacher 2008; Fredholmet al., 2011; McIntosh and Lasley, 2012; Chen et al, 2013; Headrick et al, 2013; Burnstock and Boeynaems, 2014; Burnstock, 2015; Boros et al, 2016)
This review presents an overview of cardiac A2A-adenosine receptors The localization of A2A-AR in the various cell types that encompass the heart and the role they play in force regulation in various mammalian species are depicted
Over the years a consent has emerged that A2A-AR are present and functional in the mammalian heart, more importantly in the human heart

Summary

INTRODUCTION

There have been many reviews on adenosine receptors (AR), A2A-AR (Fredholm et al, 2001; Haskó and Pacher 2008; Fredholmet al., 2011; McIntosh and Lasley, 2012; Chen et al, 2013; Headrick et al, 2013; Burnstock and Boeynaems, 2014; Burnstock, 2015; Boros et al, 2016). The present work attempts to close this gap in the literature. In their pioneering work on the pharmacology of adenosine in the heart, Drury and Szent-Györgyi (1929) showed that it can reduce the force of contraction and induce arrhythmias, namely bradycardia. The focus of the present review is the P1 receptors. A1-AR and A3-AR inhibit adenylyl cyclase, while A2A-AR and A2B-AR stimulate adenylyl cyclase activities in the heart (Olsson and Pearson, 1990)

A1 A2A A2B A3 CB1

SUMMARY