Time-Dependent Conversion of α 1- to β -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 α 1- to a...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1984-10, Vol.81 (19), p.6178-6182
Hauptverfasser: Kunos, George, Hirata, Fusao, Edward J. N. Ishac, Tchakarov, Liouben
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Sprache:eng
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Zusammenfassung: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 α 1- to a β -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 or affinity of [3H]prazosin-labeled α 1-receptors and [3H]CGP-12177-labeled β -receptors. In cells preincubated for 4 hr, a further 30min 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 β - to an α 1-receptor-mediated event, whereas in freshly isolated cells lipomodulin does not affect the predominan α -receptor response. Conversely, exposure of freshly isolated cells to a monoclonal antibody to lipomodulin in the presence of 10 μ M phenylephrine, or to melittin, an activator of phospholipase A2, at 2 μ g/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 α 1- and β -adrenoceptors to postreceptor pathways is regulated in an inverse reciprocal manner by changes in membrane phospholipase A2 activity.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.81.19.6178