a-Adrenergic Reduction of Cyclic Adenosine Monophosphate Concentrations in Rat Myocardium

We determined the effect of a-adrenergic receptor stimulation on cyclic adenosine monophosphate (cyclic AMP) concentrations in isolated myocytes derived from adult rat hearts and in isolated perfused rat hearts. Activation of a-adrenergic receptors with either phenylephrine (10~ M to 10~ M) or epinephrine (10" M to 10~ M) plus propranolol (10 ' M) resulted in a reduction in cyclic AMP levels in isolated myocytes. The action of phenylephrine was antagonized by phentolamine (10~ M). Phenylephrine (10 s M) attenuated cyclic AMP generation in response to isoproterenol (10" M and 10 s M). However, this effect of phenylephrine was not antagonized by phentolamine. Elevation of cyclic AMP concentrations produced by glucagon and by theophylline in isolated myocytes was attenuated by phenylephrine and by epinephrine plus propranolol and the attenuation was antagonized by phentolamine. In isolated perfused rat hearts epinephrine (10 (i M), when given with propranolol, diminished the rate of development of tension and also reduced tissue levels of cyclic AMP. Epinephrine alone, as well as isoproterenol, increased contractility and myocardial cyclic AMP concentrations as expected. These results indicate that catecholamines may increase or decrease cyclic AMP levels in rat myocardium, depending on the intensity of stimulation of receptor types. Increases are mediated by /3-adrenergic receptors, whereas decreases appear to be mediated by a-adrenergic receptors.