INHIBITION OF FORSKOLIN-ACTIVATED ADENYLATE-CYCLASE BY ETHANOL AND OTHER SOLVENTS

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 8  (6) , 385-394
Abstract
Ethanol and a variety of solvents are known to activate basal and Gpp(NH)p[guanylyl imidodiphosphate]- and hormone-stimulated adenylate cyclase. Ethanol and other solvents inhibit the activation of adenylate cyclase [from bovine corpora lutea] by forskolin. In the presence of 10 .mu.M forskolin, 2% ethanol gives about 20% inhibition and 5% ethanol gives 40% inhibition of enzyme activity. Analysis of ethanol inhibition at several forskolin concentrations suggests that inhibition is competitive vs. forskolin. The effect of ethanol is greater at low forskolin concentrations and minimal at high concentrations. In addition to ethanol, inhibition of forskolin activation was observed with acetone, n-butanol, tert-butanol, dimethyl formamide, dioxane, methanol and n-propanol. Dimethyl sulfoxide was inhibitory only at high concentrations (10%). Since some solvent is needed to prepare forskolin solutions and to maintain solubility at higher concentrations, the inhibitory effects are an important consideration in studies employing forskolin activation. To minimize solvent inhibition, dimethyl sulfoxide should be used to prepare forskolin solutions. At concentrations of 5% and less, dimethyl sulfoxide gives little if any inhibition of forskolin activation and causes only small increases in basal activity.