期刊
LIFE SCIENCES
卷 68, 期 22-23, 页码 2473-2479出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0024-3205(01)01041-4
关键词
muscarinic receptor; gene knockout; hypothermia; salivation; tremor; atria; muscarinic M-2; receptors; muscarinic M-4 receptors
Determination of muscarinic agonist-induced parasympathomimetic effects in wild type and M-2 and M-4 muscarinic receptor knockout mice revealed that M-2 receptors mediated tremor and hypothermia, but not salivation. The M-4 receptors seem to play a modest role in salivation, but did not alter hypothermia and tremor. In the M-2 knockout mice, agonist-induced bradycardia in isolated spontaneously beating atria was completely absent compared to their wild type litter mates, whereas agonist-induced bradycardia was similar in the M-4 knockout and wild type mice. The potency of carbachol to stimulate contraction of isolated stomach fundus, urinary bladder and trachea was reduced by a factor of about 2 in the M-2 knockout mice, but was unaltered in the M-4 knockout mice. The binding of the muscarinic agonist, [H-3]-oxotremorine-M, was reduced in cortical tissue from the M-2 knockout mice and to a lesser extent from the M-4 knockout mice, and was reduced over 90% in the brain stem of M-2 knockout mice. The data demonstrate the usefulness of knockout mice in determining the physiological function of peripheral and central muscarinic receptors. (C) 2001 Elsevier Science Inc. All rights reserved.
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