An anaesthetic dose of ethanol inhibits cyclic AMP formation by altering the function of GS protein.
The effects of ethanol on cerebral gamma-aminobutyric acid (GABA)B receptor and its related signal transduction systems were studied. [3H]GABA binding to cerebral GABAB receptors in crude synaptic membranes from rat brain was unaffected by ethanol at concentrations up to 100 mM, although 100 mM ethanol suppressed not only the basal but also forskolin-stimulated cAMP formation in cerebral cortical membrane vesicles. The suppressive effect of baclofen and the stimulatory effect of forskolin on cAMP formation was also found to be unaltered by ethanol. Pretreatment of the membrane vesicles with islet-activating protein (IAP), which eliminates the function of Gi protein by its ribosylation, had no effect on the suppressive effects of ethanol on basal and forskolin-stimulated cAMP formation. In contrast, pretreatment of membrane vesicles with 'low pH', which is known to suppress the function of Gs protein, eliminated the suppressive effect of ethanol on cAMP formation. These results suggest that an anaesthetic dose of ethanol, which is below that necessary to cause changes in receptor binding, may not affect the functions of GABAB/Gi, G(O) protein/adenylate cyclase system, but suppresses cAMP formation systems which are coupled with Gs protein.
Ichida
T
T
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Kuriyama
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000187:drug effects*; D051381:Rats; D018080:Receptors, GABA-B / Q000187:drug effects; D013570:Synaptic Membranes / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018080:Receptors, GABA-B; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases