Time course of alpha1-adrenergic and vasopressin actions on phosphorylase activation, calcium efflux, pyridine nucleotide reduction, and respiration in hepatocytes.
Calcium efflux from rat liver perfused with nonrecirculating medium was observed at 1.4 s following 10(-6) M (-)epinephrine infusion, when the perfusate Ca2+ was 60 microM. Net calcium efflux was also seen in livers perfused with 1.3 microM Ca2+ at approximately 8 s. In isolated rat hepatocytes, phosphorylase, a cytosolic enzyme, was activated significantly at 3 s and maximally at approximately 15 s by phenylephrine (10(-5) M), epinephrine (10(-6) M), and vasopressin (10(-8) M). Hexose phosphates were elevated at between 3 and 6 s with vasopressin. Phenylephrine and vasopressin stimulated hepatocyte respiration relatively slowly. The effects took 10 s to become evident, were dependent on the presence of Ca2+, and were probably the result of increased total cellular reduced pyridine nucleotide observed at 5 s. The slowness of the increase in respiration indicates that it cannot be the cause of the Ca2+ mobilization, but is more likely to be a consequence of it. From these studies, it is proposed that, following binding of catecholamines to alpha 1-adrenergic receptors, Ca2+ is first mobilized from the plasma membrane resulting in an elevation of the free Ca2+ ion concentration in the cytosol (Charest, R., Blackmore, P. F., Berthon, B., and Exton, J. H. (1983) J. Biol. Chem. 258, 8769-8773) which stimulates phosphorylase kinase and, hence, phosphorylase. These events begin to occur within the first 2 to 3 s. Following this, the concentration of reduced pyridine nucleotide(s) increases at 5 s resulting in the stimulation of respiration seen at 10 s. These events occur more slowly than the mobilization of cell Ca2+ and activation of phosphorylase, and may be secondary to the rise in cytosolic Ca2+. The time at which mitochondrial Ca2+ decreases is not known, but it accounts for most of the Ca2+ mobilized.
D000818:Animals; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D006005:Phosphorylases / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D009243:NAD; D014667:Vasopressins; D010656:Phenylephrine; D006005:Phosphorylases; D004837:Epinephrine