The effect of essential fatty acid deficiency on the adrenergic activation of glycogenolysis in rat hepatocytes.
The fatty acid composition of total lipids and the adrenoceptor-mediated activation of glycogenolysis were studied in isolated hepatocytes from rats maintained on a control diet or on an essential fatty acid (EFA)-free diet. In cells from rats on the EFA-free diet there was a marked reduction in linoleic and arachidonic acid (AA) contents and an increase in eicosatrienoic, oleic, and palmitoleic acid contents compared to controls. In freshly isolated cells from both groups, phosphorylase a activity was increased by phenylephrine or epinephrine but not by isoproterenol, and the effect of epinephrine was inhibited by phenoxybenzamine but not by propranolol. When control cells were preincubated in a serum-free buffer for 4 h before testing, the effect of phenylephrine on phosphorylase a activity was reduced, isoproterenol became a potent agonist and the effect of epinephrine was partially inhibited either by phenoxybenzamine or by propranolol. The emerging beta-adrenergic response in 4-h cells was associated with a marked potentiation of isoproterenol-induced cAMP accumulation. A similar 4-h preincubation of EFA-deficient cells resulted in a reduced response to phenylephrine while isoproterenol remained ineffective for increasing either phosphorylase a activity or cAMP production. The response of these 4-h cells to isoproterenol could be restored by in vivo replacement of the EFA-deficient diet with control diet for the last 4 weeks prior to the experiment, but not by the in vitro exposure of the EFA-deficient cells to 10 microM AA throughout the 4-h incubation period. Extending previous observations (Refs. (6-8)), the present results suggest that the time-dependent emergence of beta-adrenergic glycogenolysis, but not the parallel reduction of the alpha-adrenergic response, is mediated by AA or its metabolite(s), which probably act by facilitating the G-protein-dependent coupling of beta-receptors.
Grojec
M S
MS
Laboratory of Physiologic and Pharmacologic Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892.
Ishac
E J
EJ
Kapocsi
J
J
Kunos
G
G
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D005228:Fatty Acids, Essential / Q000172:deficiency*; D005231:Fatty Acids, Unsaturated / Q000302:isolation & purification / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008555:Melitten / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D010762:Phosphorylase a / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values
D005228:Fatty Acids, Essential; D005231:Fatty Acids, Unsaturated; D008112:Liver Glycogen; D011941:Receptors, Adrenergic; D005576:Colforsin; D010656:Phenylephrine; D008555:Melitten; D005934:Glucagon; D000242:Cyclic AMP; D010762:Phosphorylase a; D007545:Isoproterenol; D004837:Epinephrine