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Regulation of brain acetylcholine concentration by muscarinic receptors

VH Sethy and JW Francis

CNS Diseases Research, Upjohn Company, Kalamazoo, Michigan.

The cholinergic agonists oxotremorine, oxotremorine-1, oxotremorine-3, arecoline and BM 123 (N-[4-(2-chloroethylmethylamino)-2-butynyl]-2- pyrrolidone) were used to investigate the role of muscarinic receptors in the regulation of acetylcholine (Ach) concentration in the whole mouse brain. Intravenous oxotremorine, oxotremorine-1, oxotremorine-3 and arecoline dose-dependently decreased ex vivo binding of [3H]oxotremorine-M and correspondingly increased brain Ach concentration. The correlation coefficient between the ED50's of these two parameters was 0.90. BM 123 induced percentage of reduction in muscarinic receptors correlated with percentage of decrease in response of oxotremorine, for increasing brain Ach concentration. These results indicate that the muscarinic receptor system involved in the regulation of brain Ach levels may lack spare receptors.

Volume 246, Issue 1, pp. 243-248, 07/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.