The role of phosphorylation in the alpha-adrenergic-mediated inhibition of rat hepatic pyruvate kinase.
Phenylephrine in the presence of 1-methyl-3-isobutylxanthine and propanolol caused a 40-50% inhibition of pyruvate kinase (type L) activity in isolated hepatocytes, which was accompanied by a 2-3-fold increase in the phosphate content of the enzyme. These changes were blocked by the alpha-adrenergic antagonist dihydroergocryptine and could not be accounted for by the slight increase in cyclic AMP-dependent protein kinase activity generated by the alpha-adrenergic agonist. It is concluded that a significant component of the inhibition of hepatic pyruvate kinase mediated by alpha-adrenergic agonists can be attributed to a cyclic AMP-independent alteration in the phosphorylation state of the enzyme.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004088:Dihydroergotoxine / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors*; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D004088:Dihydroergotoxine; D010656:Phenylephrine; D000242:Cyclic AMP; D011494:Protein Kinases; D011770:Pyruvate Kinase