Potent Gi-mediated inhibition of adenylyl cyclase by a phosphonate analog of monooleylphosphatidate.
We have previously demonstrated that monooleylphosphatidate (MOPA) and phosphatidate inhibit adenylyl cyclase in cultured fibroblasts. In this study, the specificity of the phospholipid effect was probed by analysis of the effect of phosphonate analogs of these phospholipids on adenylyl cyclase in C6 glioma cells. The MOPA phosphonate analog inhibited adenylyl cyclase, but the comparable phosphonate analog of phosphatidate was ineffective. The IC50 for inhibition of adenylyl cyclase by the MOPA phosphonate analog was similar to that of MOPA, the maximal inhibitions were comparable (approximately 45% inhibition of hormone-stimulated adenylyl cyclase), and the effects of both appeared to be mediated by Gi, because treatment with islet-activating protein reduced the inhibition to 5-10%.
Proll
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Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston 77225.
Clark
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D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology*; D037342:Pertussis Toxin; D010712:Phosphatidic Acids / Q000494:pharmacology*; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D063065:Organophosphonates; D010712:Phosphatidic Acids; D010566:Virulence Factors, Bordetella; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D008274:Magnesium