Unsaturated fatty acids activate glycogen phosphorylase in cultured rat hepatocytes.
Oleate, linoleate, linolenate, arachidonate and eicosapentaenoate, but not myristate, palmitate and stearate, stimulated glycogen phosphorylase activity by 2-8-fold when added to cultured rat hepatocytes. Addition of BSA or Ca2- to the incubation medium decreased the stimulating effects of the unsaturated fatty acids. The combination of oleate or linolenate, with corticosterone, testosterone or estradiol produced synergistic stimulations of phosphorylase activity. The stimulation of glycogen phosphorylase activity by linolenate was inhibited by staurosporine or sphingosine. Staurosporine (80 nM) alone also decreased basal phosphorylase activities by about 60%. The results show that unsaturated fatty acids can be used as model agonists to stimulate phosphorylase activity by a mechanism that probably involves protein kinase C. On the basis of the fatty acid: BSA ratios used, this stimulation should only occur in vivo at high fatty acid concentrations when accompanied by hypoalbuminaemia.
Gomez-Muñoz
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Department of Biochemistry, University of Alberta, Edmonton, Canada.
Hales
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P
Brindley
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D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D010762:Phosphorylase a / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine; D013739:Testosterone / Q000494:pharmacology
D000470:Alkaloids; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D010762:Phosphorylase a; D006005:Phosphorylases; D011493:Protein Kinase C; D019311:Staurosporine; D013110:Sphingosine; D002118:Calcium; D003345:Corticosterone