Effects of short-chain alcohols on adenylate cyclase in plasma membranes of rat adipocytes

Summary In rat adipocyte plasma membranes the effects of methanol, ethanol, propanol-1 and butanol-1 on adenylate cyclase activity were studied in the absence (basal) and presence of maximally activating concentrations of 5-guanylylimidodiphosphate [Gpp(NH)p; 10 M] and NaF (3 mM).Basal adenylate cyclase activity increased maximally 2-fold at 0.03–0.3 M propanol or 0.01–0.1 M butanol, with increasedV_max and essentially unchangedK_m for ATP. In most experiments, methanol and ethanol had no measurable activating effect. Above appr. 0.3 M of all alcohols, basal adenylate, cyclase activity declined sharply below control values.Adenylate cyclase activity stimulated by Gpp-(NH)p was further increased severalfold by all alcohols in a concentration-dependent manner, with increasedV_max and unchanged apparentK_m for the guanyl nucleotide. The potency of the alcohols increased with chain length (1 through 4 carbons). The effect of the alcohols on Gpp(NH)p-stimulated adenylate cyclase activity was still found at concentrations where basal activity was already reduced. Adenylate cyclase activity stimulated by NaF was affected similarly but definitely less marked than Gpp(NH)p-stimulated activity.Hormone-stimulated adenylate cyclase activity expressed relative to basal enzyme activity remained essentially unaffected by the alcohols. Increase in absolute enzyme activity apparently reflected corresponding changes in basal adenylate cyclase activity.Above alcohol concentrations of 0.3 M both basal and hormone-stimulated enzyme activities were inhibited.Part of the results have been presented at the Spring Meeting of the Deutsche Pharmakologische Gesellschaft (Stock, 1977)