Diethyl ether effects on muscarinic acetylcholine receptor complexes in rat brainstem.
The influence of diethyl ether on muscarinic acetylcholine receptor-G protein interactions was studied using membranes isolated from rat brainstem. Membranes were equilibrated with diethyl ether (0.5 to 10%) for 20 min before, and then during, the binding assay. The affinity, but not the number, of [3H]N-methylscopolamine [( 3H]MS) binding sites was increased in the presence of diethyl ether (KD in air = 0.41 nM, KD in 2% diethyl ether = 0.21 nM). This increase in affinity reflected a decrease in the rapid dissociation rate constant (air k-1 = 13 X 10(-3) min-1, 2% diethyl ether k-1 = 7 X 10(-4) min-1) rather than a change in the association rate constant. Diethyl ether had no effect on the binding affinity of the muscarinic agonist carbamylcholine. However, the binding of a radiolabeled muscarinic agonist, [3H]oxotremorine-M [( 3H]Oxo-M), to high affinity binding sites decreased about 25% in the presence of 2% diethyl ether. The ability of a guanine nucleotide to depress the high affinity binding of both carbamylcholine and [3H]Oxo-M was decreased or eliminated by diethyl ether. Diethyl ether appears to interfere with muscarinic receptor-G protein interactions, perhaps by stabilizing receptor-G protein complexes or inhibiting the binding of guanine nucleotides.
D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D002217:Carbachol / Q000378:metabolism; D004986:Ether / Q000494:pharmacology*; D005019:Ethyl Ethers / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010095:Oxotremorine / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000378:metabolism
D005019:Ethyl Ethers; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D004986:Ether; D010095:Oxotremorine; D006160:Guanosine Triphosphate; D002217:Carbachol; D019204:GTP-Binding Proteins; D006221:Halothane