Effect of adenosine and catecholamines on cyclic AMP levels in guinea pig heart

Abstract

Adenosine has been shown to stimulate cyclic AMP accumulation in guinea pig atrial and ventricular slice preparations in a rapid and dose-dependent manner. Response to adenosine was inhibited by therophylline, potentiated by several other phosphodiesterase inhibitors and unaffected by alpha- or beta-adrenergic blocking agents. Agonist action required free hydroxyl groups at 2', 3', and 5' positions on the ribosyl moiety, retention of one proton on the 6-amino group, N at position 7, and unsubstituted C at position 8 on the purine moiety. The combined action between adenosine and isoproterenol was the sum of the individual stimulations. The alpha-agonist action of epinephrine and norepinephrine reduced cyclic AMP levels stimulated by beta-agonist or by adenosine; this action was mimicked by methoxamine. The effect of an alpha-agonist was particularly pronounced when cyclic AMP levels were elevated by adenosine.