Gs alpha-dependent and -independent desensitisation of prostanoid IP receptor-activated adenylyl cyclase in NG108-15 cells

European Journal of Pharmacology
R J Williams, E Kelly

Abstract

NG108-15 mouse neuroblastoma x rat glioma cells were treated with the prostanoid IP receptor agonist iloprost (1 microM) and the time course of changes in the levels of prostanoid IP receptors, adenylyl cyclase activity, and the alpha-subunit of the stimulatory guanine nucleotide binding regulatory protein, Gs, were measured. Incubation of cells with iloprost produced a biphasic time course of desensitisation of prostanoid IP receptor-activated adenylyl cyclase. Parallel analysis of iloprost-induced loss of membrane Gs alpha, NaF-stimulated adenylyl cyclase and [3H]iloprost binding suggested only monophasic curves, with t0.5 values similar to the initial phase of desensitisation of iloprost-stimulated adenylyl cyclase activity. This suggests that the loss of receptor and Gs alpha occur at the same time and account for the initial period of desensitisation due to iloprost pretreatment. Pretreatment of NG108-15 cells with cholera toxin produced a near complete loss of membrane-associated Gs alpha, but the loss of [3H]iloprost binding due to iloprost treatment was not affected by pretreatment with cholera toxin, suggesting that prostanoid IP receptors can be down-regulated in the absence of any coupling to Gs. The second phase of ...Continue Reading

References

Jun 1, 1991·Trends in Pharmacological Sciences·G Milligan, A Green
Jun 19, 1991·European Journal of Pharmacology·M KeenJ MacDermot
May 7, 1990·Biochimica Et Biophysica Acta·L BirnbaumerA M Brown
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Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·L C MahanP A Insel
Apr 1, 1974·Analytical Biochemistry·Y SalomonM Rodbell

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Citations

Jun 22, 2005·Prostaglandins & Other Lipid Mediators·Hans Meves
Apr 18, 2002·British Journal of Pharmacology·Roxana S Ghadessy, Eamonn Kelly

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