The effect of adrenaline on cardiac AMP-activated protein kinase.

Abstract

In freshly isolated adult rat cardiac myocytes, adrenaline decreased AMPK activity and Thrl72 phosphorylation in AMPK a-subunits. This was associated with a decrease in AMPK-driven phosphorylation of acetyl-CoA carboxylase. The effect of adrenaline on AMPK was rapid with a half-time of approximately 4 minutes. The inactivation of AMPK by adrenaline was not associated with detectable changes in the myocyte contents of ATP, ADP, AMP, creatine, and creatine phosphate. The effect of adrenaline on AMPK was preserved under conditions where AMPK was activated by palmitate or sorbitol, but it was markedly diminished when AMPK was activated by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), oligomycin, or phenformin. The effect of adrenaline was partially blocked by propranolol (0-adrenergic antagonist) or phentolamine (ai-adrenergic antagonist) while it was essentially abolished when both blockers were present, suggesting involvement of both p and ai adrenergic receptors. Isoproterenol (P-adrenergic agonist) and phenylephrine (ai-adrenergic agonist) could also decrease AMPK activity and Thrl72 phosphorylation. Adrenaline did not increase phosphorylation of Ser485/491 in the AMPK a-subunit, but incubation of a catalytically inactive AMPK complex (aipiyl) with a cell lysate from adrenaline-treated myocytes increased phosphorylation of the AMPK pi subunit. The effect of adrenaline was not mimicked by conditions that activated cAMP-pathways and was not blocked by an inhibitor of calcium/calmodulin-dependent kinase II. However, a phorbol ester could mimic the effect of adrenaline on AMPK, suggesting the possible involvement of PKC isoforms