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Effects of Chronic Ethanol Treatment on the β‐Adrenergic Receptor‐Coupled Adenylate Cyclase System of Mouse Cerebral Cortex
Author(s) -
Saito Toshikazu,
Lee John M.,
Hoffman Paula L.,
Tabakoff Boris
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb05741.x
Subject(s) - cyclase , adenylate kinase , medicine , endocrinology , stimulation , chemistry , ethanol , receptor , cerebral cortex , biology , biochemistry
Chronic ingestion of ethanol, which produced tolerance and physical dependence, resulted in altered function of the cerebral cortical β‐adrenergic receptor‐coupled adenylate cyclase system in mice. Although there was no change in basal adenylate cyclase activity, or in the activity of the digitonin‐solubilized catalytic unit, stimulation of adenylate cyclase activity by the nonhydrolyzable guanine nu‐cleotide analog guanylylimidodiphosphate [Gpp(NH)p] was reduced in brains of ethanol‐fed animals. Ethanol added in vitro increased adenylate cyclase activity, and this enhancement, in the presence of Gpp(NH)p, was also reduced in cortical membranes of ethanol‐fed mice. Furthermore, the maximal response to isoproterenol was decreased, and the EC 50 for isoproterenol stimulation of adenylate cyclase activity was increased in ethanol‐fed animals. The results are consistent with a qualitative or quantitative defect in the function of the stimulatory guanine nucleotide‐bind‐ing protein (N s ), as well as in the β‐adrenergic receptor, after chronic ethanol exposure. In part, these changes appear to be similar to those that occur during heterologous desensiti‐zation of various receptor systems, and may be associated with dependence on or tolerance to ethanol.