Alpha 1-adrenergic regulation of ketogenesis in isolated rat hepatocytes.
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.
Nomura
T
T
Department of Pharmacology, Fujita Health University School of Medicine, Aichi, Japan.
Nomura
Y
Y
Tachibana
M
M
Nomura
H
H
Ukai
K
K
Yokoyama
R
R
Hagino
Y
Y
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
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