Activation of adenylate cyclase by ethanol in mouse striatal tissue.
The effects of ethanol on adenylate cyclase activity were investigated in homogenates of mouse striatum. Ethanol (34--340 mM) elicited a linear increase in basal and dopamine-stimulated adenylate cyclase activities. The increase in dopamine-stimulated activity was statistically significant at ethanol concentrations of 68 mM and above. The increase in maximal adenylate cyclase activity observed in the presence of ethanol was not entirely due to the increase in basal activity. In the presence of 100 and 300 mM ethanol maximal adenylate cyclase activities were increased by 26 and 71% even after correcting for the increase in basal activity. The concentration of dopamine required for half-maximal activation was not changed by the presence of ethanol. Activation of adenylate cyclase by ethanol was found to be reversible and was not blocked by the dopaminergic antagonist butaclamol, the alpha adrenergic antagonist phentolamine or the beta adrenergic antagonist propranolol. Concentrations of ethanol of up to 500 mM did not change either the affinity of the receptor for [3H]-spiroperidol or the density of binding sites. A decrease in the affinity of the receptor for the radioligand was observed at higher concentrations of ethanol. The affinity of the receptor for dopamine was decreased by 2-fold in the presence of 300 mM ethanol. Addition of 300 microM GTP elicited a 5-fold decrease in the affinity o the receptor for dopamine in both the presence and absence of ethanol. The activation of adenylate cyclase by ethanol was not unique to striatal tissue. In studies carried out with homogenates of cerebral cortex and cerebellum, addition of ethanol increased basal, isoproterenol-stimulated and sodium fluoride-stimulated activities. The results show that pharmacologically relevant concentrations of ethanol can alter adenylate cyclase activity.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011954:Receptors, Dopamine / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
D011954:Receptors, Dopamine; D000431:Ethanol; D013134:Spiperone; D000262:Adenylyl Cyclases