CAMP AND PROTEIN-SYNTHESIS IN ISOLATED ADULT-RAT HEART PREPARATIONS

The involvement of adenosine 3',5'-cyclic monophosphate (cAMP) in the stimulation of ventricular protein synthesis by aortic hypertension or adrenergic agonists in the adult rat heart was investigated. In eithe r the retrogradely or anterogradely perfused heart, aortic hypertensio n increased protein synthesis rates by up to 19%. However, no changes in cAMP concentrations or in cAMP-dependent protein kinase activity ra tios could be detected either at early (<5 min) or late (90 min) time points. Although isoproterenol, 3-isobutyl-1-methylxanthine, or forsko lin raised cAMP concentrations (by up to 4.5-fold) and cAMP-dependent protein kinase ratios (by up to 4-fold), protein synthesis rates were not increased; however, under some perfusion conditions, glucagon did stimulate protein synthesis by 25%. Epinephrine stimulated protein syn thesis by up to 32%, an effect that was not prevented by propranolol. Phenylephrine also stimulated protein synthesis, an effect that was pr evented by prazosin but was unaffected by yohimbine. These findings im plicate the al-adrenoceptor in the regulation of cardiac protein synth esis. Because changes in adenine nucleotide concentrations were simila r in hearts perfused with epinephrine or with the agents that raised c AMP, it is unlikely that adenine nucleotide depletion is responsible f or the failure to observe effects of the latter group of agents on pro tein synthesis. Although isoproterenol or forskolin raised cAMP concen trations in isolated ventricular cardiomyocytes where ATP depletion wa s minimal, neither stimulated protein synthesis. Alpha1-Adrenergic ago nists stimulate phosphoinositide hydrolysis in the heart (Brown, J. H. , I. L. Buxton, and L. L. Brunton. Circ. Res. 57: 532-537, 1985). Aort ic hypertension doubled the rate of phosphoinositide hydrolysis in the perfused heart. We suggest that the phosphoinositide-linked signal tr ansduction pathway is more likely to be involved in stimulation of car diac protein synthesis by hypertension or adrenergic agonism than the adenylyl cyclase/cAMP-linked pathway.