Studies on alpha-adrenergic-induced respiration and glycogenolysis in perfused rat liver.
Phenylephrine (1.5 x 10(-6) M) administered to perfused livers from fed rats gave rise to a rapid, parallel increase in oxygen uptake and glucose output. The time of onset for oxygen uptake was 9.9 +/- 0.4 s following phenylephrine administration, and immediately preceded glucose output which occurred at 11.6 +/- 0.5 s. Near-maximal effects were observed 50 s following alpha-agonist treatment. Both responses appear to be mediated by alpha- 1-adrenergic receptors. The mitochondrial respiratory chain blockers antimycin A and rotenone, inhibited the alpha-agonist-induced oxygen uptake and glycogenolytic responses at inhibitor concentrations similar to those required to block uncoupler-stimulated respiration in the intact perfused liver. Oligomycin and carboxyatractyloside also inhibited the phenylephrine-induced respiratory response. Vasopressin (1 milliunit/ml), and angiotensin II (6 x 10(-9) M) had effects similar to phenylephrine in the perfused liver which also were prevented by the prior administration of antimycin A and rotenone. In contrast, glucagon-induced (10(-8) M) glycogenolysis proceeded in the absence of large changes in respiration, was slower in onset (26.1 +/- 4.2 s following hormone administration), and was not inhibited by mitochondrial respiratory blockers. These data indicate that glycogenolysis induced by alpha-adrenergic agonists, vasopressin, and angiotensin II is associated with a large increase in mitochondrial respiration, that may play a role in a general, as yet undefined mechanism whereby these agents stimulate glycogenolysis in rat liver.
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D004140:Dinitrophenols; D008112:Liver Glycogen; D012402:Rotenone; D010656:Phenylephrine; D015016:Yohimbine; D000968:Antimycin A; D005934:Glucagon; D011224:Prazosin