Reduction by adenosine of the isoproterenol-induced increase in cyclic adenosine 3',5'-monophosphate formation and glycogen phosphorylase activity in rat heart muscle.

Abstract

The effect of adenosine on the increase in cardiac cyclic(c)AMP concentration and glycogen phosphorylase activity produced by isoproterenol was investigated. Slices of rat ventricular myocardium 0.5 mm thick weighing 15-20 mg were cut, washed and incubated at 37.degree. C in physiological saline gassed with either O2 (oxygenated) or N2 (anoxia). The concentration of cAMP declined as the time of incubation increased in both oxygenated and anoxic muscle. In oxygenated muscle, isoproterenol, 10 .mu.M, produced a 2.2-fold increase in cAMP concentration and phosphorylase activity. Adenosine at 1 .mu.M caused a 35% and 75% reduction in the isoproterenol-produced increase in cAMP concentration and phosphorylase activity, respectively, without affecting basal levels. Reduction of the isoproterenol-elicited increase in cAMP occurred within 2 min. Adenosine alone only at a high concentration of 1 mM increased cAMP by 38% in oxygenated muscle. Adenine and inosine did not mimic the effect of adenosine on the isoproterenol-induced augmentation of cAMP. Addition of adenosine deaminase to the physiological saline prevented the effects of adenosine but did not affect basal cAMP. In anoxic tissue, isoproterenol failed to produce an increase in cAMP and phosphorylase. Addition of adenosine deaminase to anoxic tissue resulted in an isoproterenol-produced increase in cAMP, indicating that adenosine may inhibit an isoproterenol-induced increase in cAMP during anoxia. Adenosine attenuates the catecholamine-induced increase in cAMP concentration and phosphorylase activity in oxygenated cardiac muscle, but in the anoxic myocardium, adenosine may be responsible for preventing an increase in cAMP on .beta.-adrenergic stimulation. Adenosine may antagonize catecholamine elicited glycogenolysis.