Time-dependent conversion of alpha 1- to beta-adrenoceptor-mediated glycogenolysis in isolated rat liver cells: role of membrane phospholipase A2.
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 a glycogenolytic response to isoproterenol within 4 hr. This conversion of the adrenergic activation of phosphorylase from an alpha 1- to a beta-adrenoceptor-mediated response is associated with no change in the glycogenolytic response to the calcium-linked activator vasopressin, and a reduction of the glycogenolytic response to the cAMP-linked activator glucagon. In vitro incubation of hepatocytes does not influence the density of affinity of [3H]prazosin-labeled alpha 1-receptors and [3H]CGP-12177-labeled beta-receptors. In cells preincubated for 4 hr, a further 30-min incubation with 50 nM lipomodulin, an endogenous inhibitor of membrane phospholipase A2 (EC 3.1.1.4), reverses the adrenergic activation of phosphorylase from a beta- to an alpha 1-receptor-mediated event, whereas in freshly isolated cells lipomodulin does not affect the predominant alpha-receptor response. Conversely, exposure of freshly isolated cells to a monoclonal antibody to lipomodulin in the presence of 10 microM phenylephrine, or to melittin, an activator of phospholipase A2, at 2 micrograms/ml, results in the suppression of the effect of phenylephrine and the emergence of a response to isoproterenol within 30 min. It is proposed that coupling of hepatic alpha 1- and beta-adrenoceptors to postreceptor pathways is regulated in an inverse reciprocal manner by changes in membrane phospholipase A2 activity.
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D005934:Glucagon / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology
D008112:Liver Glycogen; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014667:Vasopressins; D010656:Phenylephrine; D005934:Glucagon; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D007545:Isoproterenol