Ethanol disruption of muscarinic acetylcholine receptor-G protein interactions in rat brainstem revealed by ligand binding measurements

R. S. Aronstam, R. L. Dennison, D. C. Martin, R. Ravindra

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The influence of ethanol on the interaction of muscarinic acetylcholine receptors with transducer G proteins was investigated in agonist binding studies. Ethanol decreased agonist binding affinities at 4°C but increased agonist affinities at 37°C. The ability of a guanine nucleotide, 5'-guanylylimidodiphosphate, to convert receptors from a high affinity, G protein-coupled state to a low affinity, uncoupled state at 20°C was greatly diminished by ethanol at concentrations as low as 50 mM. This effect was apparent in both carbamylcholine/[3H]N-methylscopolamine competition studies and direct measurements of high affinity [3H]oxotremorine-M binding. The ability of a series of n-alkanols to reduce the guanine nucleotide sensitivity of [3H]oxotremorine-M binding increased with the length of the alkyl chain. These results suggest that a disruption of receptor-G protein interactions plays a role in the depression of muscarinic synaptic transmission by ethanol, and may contribute to the effects of ethanol during intoxication.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalNeuroscience Research Communications
Volume12
Issue number3
Publication statusPublished - Jan 1 1993

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Keywords

  • Acetylcholine
  • Ethanol
  • G proteins
  • Muscarinic receptors
  • Receptor-G protein coupling

ASJC Scopus subject areas

  • Neuroscience(all)

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