Cyclic AMP-induced desensitization of G-protein-regulated phospholipase C in turkey erythrocyte membranes

European Journal of Pharmacology
M C Galas, T K Harden

Abstract

The interaction of the cyclic AMP and inositol lipid signalling systems was studied in turkey erythrocytes. Elevation of intracellular cyclic AMP concentrations by pretreatment of the cells with forskolin or 8-Br-cAMP resulted in a marked decrease in responsiveness of phospholipase C to G-protein activators in membranes prepared from treated cells. Decreases in responsiveness occurred with a t1/2 of approximately 5 min and were reversible after transfer of desensitized cells to drug-free medium. Pretreatment of the cells with forskolin inhibited inositol phosphate formation in a concentration-dependent manner and addition of the phosphodiesterase inhibitor IBMX 93-isobutyl-1-methylxanthine) during pretreatment increased the capacity of forskolin to desensitize phospholipase C activity. IBMX also produced a similar potentiation of forskolin-stimulated accumulation of cyclic AMP in turkey erythrocytes. Isoproterenol pretreatment of the cells induced, like forskolin, partial inhibition of inositol phosphate generation in response to G-protein activators and to P2y purinoceptor and beta-adrenoceptor agonists. The capacity of isoproterenol to induce desensitization of phospholipase C activity also was increased by the presence of IB...Continue Reading

References

May 1, 1990·Trends in Pharmacological Sciences·R J LefkowitzM G Caron
Jun 1, 1987·Journal of Cellular Physiology·R W GodfreyS T Hoffstein
Apr 1, 1974·Analytical Biochemistry·Y SalomonM Rodbell
Sep 17, 1984·Biochemical and Biophysical Research Communications·R LabarcaS M Paul
Jul 1, 1993·Trends in Pharmacological Sciences·R J WojcikiewiczS R Nahorski
Oct 15, 1995·European Journal of Pharmacology·M C Galas, T K Harden

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Citations

Nov 9, 2000·European Journal of Pharmacology·N ParameswaranW S Spielman
Nov 11, 2006·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Piero BagnaresiCélia R S Garcia
Feb 19, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Michael J WassermanJerry J Warsh

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