Time dependent conversion from alpha 1- to beta-adrenoceptor-mediated glycogenolysis in isolated rat hepatocytes: role of membrane phospholipase A2 and protein kinase C.
1. Incubation of isolated rat liver cells in a serum-free buffer leads to the reduction of the glycogenolytic effect of phenylephrine and the simultaneous emergence of the response to isoprenaline within 4 h. 2. Inhibitors of phospholipase A2 reverse the adrenergic activation of phosphorylase alpha from a beta- to an alpha 1-receptor-mediated event. Conversely activators of phospholipase A2 enhance the conversion. 3. In vitro incubation of hepatocytes leads to a translocation of protein kinase C from the cytosol to the membrane which can be mimicked by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C. PMA is also associated with transformation from alpha 1- to beta-adrenoceptor-mediated glycogenolysis. 4. It is proposed that coupling of hepatic alpha 1- and beta-adrenoceptors to postreceptor pathways are regulated by changes in membrane phospholipase A2 and protein kinase C activity.
Ishac
E J
EJ
Department of Pharmacology, McGill University, Montreal, Quebec, Canada.
Kunos
G
G
D000818:Animals; D002478:Cells, Cultured; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D010741:Phospholipases A / Q000502:physiology; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013997:Time Factors
D008112:Liver Glycogen; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2