BLOCKADE OF ADENOSINE RECEPTORS UNMASKS A STIMULATORY EFFECT OF ATP ON CARDIAC CONTRACTILITY

1 The effects of ATP, alpha,beta-methylene ATP and beta,gamma-methylen e ATP on the contractile tension of guinea-pig isolated left atria wer e evaluated. 2 ATP (1- 100 muM) produced a concentration-dependent neg ative inotropic effect; this response was converted to a positive inot ropic effect in the presence of the antagonist of adenosine A1 recepto rs, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 0.1 muM), and in the pr esence of 8-phenyltheophylline (10 muM), an antagonist of Al and A2 re ceptors. 3 The positive inotropic effect of ATP was antagonized by the P2 receptor antagonist, suramin (500 muM). Reactive blue 2 (30-500 mu M), a putative P2y receptor antagonist, concentration-dependently redu ced and finally abolished the effect of ATP. 4 In the presence of 8-ph enyltheophylline, the stable analogues of ATP, alpha,beta-methylene AT P and beta,gamma-methylene ATP (1 - 30 muM), produced a concentration- dependent increase in atrial contractility of a lesser degree than tha t induced by ATP. 5 The results suggest that when inhibitory adenosine receptors are blocked, ATP produces a positive inotropic effect, prob ably mediated by P2y receptor stimulation.