Inhibition of adenylate cyclase by p-bromophenacyl bromide.
p-Bromophenacyl bromide (BPB) is an alkylating agent which has been used in biochemical studies as an inhibitor of phospholipase A2 activity. We report here that BPB irreversibly inhibited adenylate cyclase activity stimulated by hormones, forskolin, GppNHp, NaF, and cholera toxin. The action of BPB in S49 lymphoma cell membranes (wild type and cyc-) indicates that it can inhibit adenylate cyclase function in the absence of Gs. In the presence of Gs, however, inhibition of adenylate cyclase by BPB was enhanced, suggesting that BPB may covalently modify the catalytic protein on a site involved in activated catalytic functioning or critical to its interaction with Gs and/or additionally on the alpha s protein.
O'Donnell
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Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, MO 63104.
Howlett
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D000098:Acetophenones / Q000494:pharmacology*; D000067956:Adenylyl Cyclase Inhibitors; D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D012633:Secretin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000098:Acetophenones; D000067956:Adenylyl Cyclase Inhibitors; D000477:Alkylating Agents; D012633:Secretin; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; C006821:4-bromophenacyl bromide