title: Alpha 1-adrenergic regulation of ketogenesis in isolated rat hepatocytes.
abstract: Studies were conducted to clarify the effects of noradrenaline on oleate metabolism in isolated hepatocytes from fed rats. Noradrenaline caused an inhibition of ketogenesis from oleate along with a stimulation of glucose release through alpha 1-adrenergic receptors. Anti-ketogenic action of noradrenaline was confirmed by the suppression of the formation of radioactive acid-soluble products from [1-14C]oleate in response to this agent. Noradrenaline increased the conversion of [1-14C]oleate into 14CO2 but failed to affect [1-14C]oleate esterification. When hepatocytes were incubated in a medium containing 1 mM EGTA but no Ca2+, the effects of noradrenaline on oleate oxidation were negated. On the other hand, noradrenaline-induced increase in glucose release remained unchanged even in the absence of Ca2+ in the incubation medium. Decrease in ketogenesis and increase in glucose release produced by vasopressin was completely abolished by calcium depletion. Noradrenaline caused a significant increase in cAMP levels in both the presence and absence of Ca2+, although the effect was more marked in the latter. Vasopressin did not affect it. The noradrenaline-induced increase in cAMP and glucose release in the absence of Ca2+ was also mediated by alpha 1-adrenergic receptors. These data are discussed and it is suggested that alpha 1-adrenergic agonists may control hepatic ketogenesis and glycogenolysis through two separate signal transduction mechanisms, i.e., a calcium-mobilizing system which is common with vasopressin, and a cAMP generation system which vasopressin lacks.
authors.affiliation: Department of Pharmacology, Fujita Health University School of Medicine, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: Y
authors.initials: Y
authors.lastname: Nomura
authors.forename: M
authors.initials: M
authors.lastname: Tachibana
authors.forename: H
authors.initials: H
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Ukai
authors.forename: R
authors.initials: R
authors.lastname: Yokoyama
authors.forename: Y
authors.initials: Y
authors.lastname: Hagino
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D007657:Ketone Bodies; D009829:Oleic Acids; D011942:Receptors, Adrenergic, alpha; D014667:Vasopressins; D010656:Phenylephrine; D019301:Oleic Acid; D003994:Bucladesine; D005934:Glucagon; D005947:Glucose; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine