Adenosine enhancement of adrenergic neuroeffector transmission in guinea-pig pulmonary artery

Abstract

1. Adenosine and its derivatives N6-[(R)-1-methyl-2-phenylethyl]adenosine (R-PIA) or 5'-N-ethyl-carboxamideadenosine (NECA) enhanced nerve-induced contractile responses and augmented the basal smooth muscle tone in transmurally stimulated isolated strips of the guinea-pig pulmonary artery. 2. Adenosine, R-PIA and NECA enhanced contractile responses induced by noradrenaline, whereas N6-[(S)-1-methyl-2-phenylethyl]-adenosine (S-PIA) was virtually inactive. 3. Adenosine, R-PIA and NECA inhibited the nerve stimulation evoked release of [3H]-noradrenaline. However, the total release of [3H]-noradrenaline during the periods of NECA application was increased. 4. The nucleoside effects were blocked by the adenosine receptor antagonist 8-p-sulphophenyltheophylline. 5. 8-p-Sulphophenyltheophylline inhibited nerve-induced contractions and lowered basal muscle tone in preparations not having received any exogenous purines. 6. It is suggested that the observed stimulatory effects on muscle tone and on contractile responses to transmural nerve stimulation are mainly due to action at postjunctional stimulatory A1 adenosine receptors. In addition, actions at prejunctional inhibitory A1 and stimulatory A2 adenosine receptors are evident in this preparation.