PMID: 3773884Nov 1, 1986Paper

Effect of cholera toxin on the activation of adenylate cyclase by calmodulin in bovine striatum

Molecular Pharmacology
C K MickeviciusM E Gnegy

Abstract

The effect of cholera toxin on activation of adenylate cyclase by the endogenous Ca2+-binding protein, calmodulin, GTP, dopamine, and forskolin was investigated in bovine striatum. Adenylate cyclase activity was measured in washed membrane fractions prepared from homogenates that had been preincubated with cholera toxin. Pretreatment of striatal membranes with cholera toxin increased the response of adenylate cyclase to GTP, calmodulin, and forskolin as compared to vehicle controls. After cholera toxin pretreatment, the maximal response of adenylate cyclase to GTP was increased 4.7-fold and the apparent Ka for GTP was reduced 3-fold. The apparent Vmax for calmodulin was doubled after cholera toxin pretreatment. The activation of adenylate cyclase by forskolin was increased by cholera toxin, but the effect on kinetic parameters was not determined due to solubility considerations. In contrast, dopamine-stimulated adenylate cyclase activity was abolished after cholera toxin pretreatment. Examination of a concentration-response curve for cholera toxin in altering these activities revealed that calmodulin-stimulated adenylate cyclase was maximally affected at lower concentrations of cholera toxin than was activation by GTP and forsk...Continue Reading

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