Chronic in vivo ethanol administration alters the sensitivity of adenylate cyclase coupling in homogenates of rat brain.
The high activities of adenylate cyclase, phosphodiesterase and protein kinases in the synaptic terminals of the central nervous system makes these enzymes prime candidates for the in vivo actions of ethanol. Adult female rats were fed a liquid diet containing ethanol as 35% of the available calories for 6 days. This resulted in a decrease (22-45%) in the basal activity of adenylate cyclase, as determined by cyclic 3',5'-adenosine monophosphate (cAMP) production, in homogenates of all brain areas tested. In these homogenates the ability of guanosine triphosphate and noradrenaline to stimulate basal cyclase activity was severely reduced. These results suggest that ethanol administration causes an uncoupling of the beta-receptor/adenylate cyclase cascade and an interruption of the control of the synthesis of cAMP.
Saffey
K
K
MRC Brain Metabolism Research Group, University of The Witwatersrand Medical School, Johannesburg, South Africa.
Gillman
M A
MA
Cantrill
R C
RC
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000431:Ethanol; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D009638:Norepinephrine