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

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.