The effect of ethanol on muscarinic receptor-G protein coupling in the rat cortex
To understand the mechanism of ethanol action on G protein-mediated signal transduction pathway, the effect of ethanol on muscarinic receptor-G protein coupling in the rat cerebral cortex was examined. Acetylcholine (ACh)-stimulated G protein GTPase activity was used as an index of receptor-G protei...
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Published in | Pharmacology & toxicology Vol. 81; no. 6; p. 294 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Denmark
01.12.1997
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Abstract | To understand the mechanism of ethanol action on G protein-mediated signal transduction pathway, the effect of ethanol on muscarinic receptor-G protein coupling in the rat cerebral cortex was examined. Acetylcholine (ACh)-stimulated G protein GTPase activity was used as an index of receptor-G protein coupling. ACh stimulation of G protein GTPase activity was time- and concentration-dependent, and atropine-sensitive. Rats injected with ethanol (3 g/kg body weight) were sacrificed after 4 hr, and the cerebral cortices removed. The ability of ACh to stimulate GTPase activity was similar in cortical cell membranes obtained from control and ethanol-treated rats; ACh maximally stimulated the enzymatic activity by 22% in membranes from both groups of rats. Next, in cortical cell membranes obtained from control rats (i.e., not injected with ethanol) the ability of ACh to stimulate GTPase activity in the presence of ethanol was examined. ACh stimulated GTPase activity in a concentration-dependent manner; the activity was 12.3 +/- 0.1, 14.5 +/- 0.64, 15.7 +/- 0.54, and 16.1 +/- 0.33 Pi pmol/min/mg protein, at 0, 0.01, 0.1, and 1 mM ACh, respectively (P < 0.05). In the presence of 100 mM ethanol ACh-stimulated GTPase activity was significantly inhibited. The IC50 value of ethanol inhibition of ACh-stimulated GTPase activity was approximately 50 mM. These results suggest that: 1) in vitro, ethanol impairs ACh-stimulated G protein GTPase activity in the rat cortical cell membranes, and 2) in vivo, the acute effects of alcohol on G protein function may be transient and reversible. |
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AbstractList | To understand the mechanism of ethanol action on G protein-mediated signal transduction pathway, the effect of ethanol on muscarinic receptor-G protein coupling in the rat cerebral cortex was examined. Acetylcholine (ACh)-stimulated G protein GTPase activity was used as an index of receptor-G protein coupling. ACh stimulation of G protein GTPase activity was time- and concentration-dependent, and atropine-sensitive. Rats injected with ethanol (3 g/kg body weight) were sacrificed after 4 hr, and the cerebral cortices removed. The ability of ACh to stimulate GTPase activity was similar in cortical cell membranes obtained from control and ethanol-treated rats; ACh maximally stimulated the enzymatic activity by 22% in membranes from both groups of rats. Next, in cortical cell membranes obtained from control rats (i.e., not injected with ethanol) the ability of ACh to stimulate GTPase activity in the presence of ethanol was examined. ACh stimulated GTPase activity in a concentration-dependent manner; the activity was 12.3 +/- 0.1, 14.5 +/- 0.64, 15.7 +/- 0.54, and 16.1 +/- 0.33 Pi pmol/min/mg protein, at 0, 0.01, 0.1, and 1 mM ACh, respectively (P < 0.05). In the presence of 100 mM ethanol ACh-stimulated GTPase activity was significantly inhibited. The IC50 value of ethanol inhibition of ACh-stimulated GTPase activity was approximately 50 mM. These results suggest that: 1) in vitro, ethanol impairs ACh-stimulated G protein GTPase activity in the rat cortical cell membranes, and 2) in vivo, the acute effects of alcohol on G protein function may be transient and reversible. |
Author | Depala, V Gao, Y McIlroy, P J Singh, S P Ravindra, R Handa, R K |
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SubjectTerms | Acetylcholine - pharmacology Animals Binding Sites Cell Membrane - drug effects Central Nervous System Depressants - toxicity Cerebral Cortex - drug effects Cerebral Cortex - metabolism Dose-Response Relationship, Drug Ethanol - toxicity GTP Phosphohydrolases - metabolism GTP-Binding Proteins - metabolism Male Rats Rats, Sprague-Dawley Receptors, Muscarinic - drug effects Receptors, Muscarinic - metabolism |
Title | The effect of ethanol on muscarinic receptor-G protein coupling in the rat cortex |
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