Acute effect of epinephrine on muscle proteolysis in perfused rat hindquarters

Abstract

An acute and direct effect of epinephrine (Epi) on muscle proteolysis was investigated using a single-pass mode of rat hindquarter perfusion. The rate of tyrosine (Tyr) release at > 30 min with cycloheximide was regarded as the muscle proteolytic rate. Infusion of Epi (500 nM) to the hindquarters of fed rats led to a sharp decrease in the Tyr release to 50% within 5 min, accompanied by an increase in perfusion pressure and edema around the perfused tissues. To clarify the mechanism, alpha- and beta-antagonists were used together with Epi. A mixture of 10 microM prazosin and 10 microM yohimbine (alpha-adrenergic blockade) before or after Epi infusion completely prevented the edema development and resulted in a new steady state to 80% of the initial rate. On the contrary, 100 microM propranolol (a beta-antagonist) with Epi did not abolish the edema and caused fluctuation in Tyr release. Whether the above results are affected by changes in Tyr transport at the plasma membrane was tested by measuring Tyr efflux from the perfused muscle. Only a beta-adrenergic blockade significantly reduced the rate constant of Tyr efflux from the intracellular pool by 13%. These results suggested that the suppression of Tyr release by alpha-adrenergic activity was mainly due to the effect on Tyr efflux, whereas that by beta-adrenergic activity was not at the Tyr transport level but at the proteolysis level, demonstrating that Epi directly inhibits proteolysis of skeletal muscle via the beta-adrenoceptor.