Differential effects of ethanol on the striatal and cortical adenylate cyclase system.

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概要

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• In the present study, effects of ethanol (EtOH) on C57/BL mouse cortical β-adrenergic receptor coupled adenylate cyclase (AC) were shown to be different from the effects of EtOH on striatal dopaminergic-stimulated AC activity. The addition of EtOH (500 mM) increased the AC activity by 60% in cortical membrane and by less than 10% in striatal membrane preparations in the absence of guanine nucleotide. The dose-response relationship for EtOH stimulation of cortical AC activity in the presence of guanylylimidodiphosphate (Gpp(NH)p) was biphasic, whereas, in the striatum, a linear dose-response relationship for EtOH was found for stimulation of AC in the presence of Gpp(NH)p. Activation of AC by Gpp(NH)p occurred as an apparent pseudo-first order process. EtOH increased the pseudo-first order rate constant for activation of AC by Gpp(NH)p in the cortex, but not in the striatum. Following 10 min preincubation with Gpp(NH)p, catecholamines and Gpp(NH)p were not able to stimulate further the AC activities in either tissue. Nevertheless, EtOH increased AC activity in both cortex and striatum following the preincubation with Gpp(NH)p. These data suggest that one effect of EtOH in striatal tissue is to promote the interaction of an activated guanine nucleotide-binding regulatory protein (G-protein) with the catalytic unit of AC. In cortical tissue, the effects of EtOH may be attributable to direct actions on the catalytic activity of the enzyme, effects on the rate of activation of the G-protein, and an altered interaction of G-protein with the catalytic unit.

• 公益社団法人 日本薬理学会の論文

著者

• Lee John

  Department Of Animal And Plant Sciences The University Of Sheffield

• Saito Toshikazu

  Department Of Diabetes And Endocrinology Social Insurance Central General Hospital

• HOFFMAN Paula

  National Institute on Alcohol Abuse and Alcoholism

• LUTHIN Gary

  Department of Pharmacology, University of Pennsylvania

• TABAKOFF Boris

  National Institute on Alcohol Abuse and Alcoholism

• SAITO Toshikazu

  Department of Neuropsychiatry, Sapporo Medical College

• LEE John

  Department of Physiology and Biophysics, University of Illinois at Chicago

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