Role of A2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

Authors:
Publisher website
Google Scholar
Abstract
Adenosine‐5′‐triphosphate (ATP) and adenosine are potent coronary vasodilators. ATP is rapidly converted to adenosine by ectonucleotidases. We examined whether coronary vasodilation caused by exogenous ATP is mediated by P2 receptor activation or by A2A‐adenosine receptor activation. Effects of interventions on coronary conductance were determined by measuring coronary perfusion pressure in guinea‐pig isolated hearts perfused at a constant flow of 10 ml min−1. ATP and adenosine both caused sustained, concentration‐dependent increases of coronary conductance. Maximal responses to both agonists were equivalent. The values of pD2 (±s.e.mean) for ATP and adenosine were 6.68±0.04 and 7.06±0.05, respectively. Adenosine was significantly more potent than ATP (Pn=10). The values of pIC50 for the selective A2A‐adenosine receptor antagonist SCH58261 to antagonize equivalent responses to ATP and adenosine were 8.28±0.08 and 8.28±0.06 (P=0.99, n=6), respectively. The non‐selective adenosine receptor antagonists xanthine amine congener (XAC) and CGS15943 antagonized similarly the equivalent vasodilations caused by ATP (pIC50 values 7.48±0.04 and 7.45±0.06, respectively) and adenosine (pIC50 values 7.37±0.13 and 7.56±0.11). In contrast to ATP and adenosine, the two P2 agonists 2‐methylthio‐ATP and uridine‐5′‐triphosphate failed to cause stable increases of coronary conductance, caused desensitization of vasodilator responses, and were not antagonized by SCH 58261, 8‐parasulphophenyltheophylline, or XAC. Glibenclamide attenuated coronary vasodilations caused by ATP and adenosine by 88 and 89%, respectively, but failed to attenuate those caused by 2‐methylthio‐ATP. These results strongly suggest that sustained, submaximal coronary vasodilation caused by exogenous ATP is entirely mediated by adenosine acting upon A2A‐adenosine receptors. British Journal of Pharmacology (2000) 130, 1065–1075; doi:10.1038/sj.bjp.0703386

This publication has 55 references indexed in Scilit: