Beta-adrenergic receptor binding in brain of alcoholics.
The binding of agonists and antagonists to beta-adrenergic receptors in brain tissue obtained postmortem in nonalcoholic controls and matched intoxicated and sober alcoholics was measured to assess the state of the receptors and their coupling to adenylate cyclase. Binding of antagonist, iodocyanopindolol, to cerebral cortical and cerebellar membrane preparations was not different in alcoholics compared to that in controls, suggesting that the number of beta-adrenergic receptors was not affected by chronic ethanol ingestion. Agonist binding data, however, indicated the loss of the high-affinity agonist binding state of the beta-adrenergic receptor, representing the receptor-guanine nucleotide binding protein (Gs) complex. Such changes were observed in cerebral cortex but not in cerebellum of intoxicated alcoholics. These data suggest that cerebral cortical beta-adrenergic receptors are uncoupled from adenylate cyclase in these subjects. In cerebral cortical and cerebellar membranes of sober alcoholics both the high- and low-affinity agonist binding sites were observed. These findings are similar to those seen in animal studies and suggest that the effect of chronic ethanol ingestion on beta-adrenergic receptor-adenylate cyclase coupling is brain region specific and reversible with abstinence. Ethanol-induced changes in the coupling of receptors to adenylate cyclase may contribute to the physiological and behavioral manifestations of alcohol abuse.
Valverius
P
P
Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892.
Borg
S
S
Valverius
M R
MR
Hoffman
P L
PL
Tabakoff
B
B
D000435:Alcoholic Intoxication / Q000378:metabolism*; D000437:Alcoholism / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol