Wakade A R, Kahn R, Malhotra R K, Wakade C G, Wakade T D
Life Sci. 1986 Dec 1;39(22):2073-80. doi: 10.1016/0024-3205(86)90358-9.
Pirenzepine, McN-A-343 and oxotremorine were used to determine the subtypes of muscarinic receptors involved in the secretion of catecholamines from the isolated perfused adrenal gland of the rat. In the presence of 0.1 microM pirenzepine, the concentration-secretion curve for muscarine was shifted in parallel to the right by almost one log unit. With 0.5 microM the shift was over two log units. The apparent dissociation constant for pirenzepine was about 1.12 X 10(-8) M. Perfusion with McN-A-343 (1-30 microM) did not evoke the secretion of catecholamines. A further increase to very high concentrations (100-1000 microM) caused only a modest secretion (about 50 ng/5 min with 300 microM as compared to the same amount of secretion obtained with 1 microM muscarine). Secretion evoked by nicotine was significantly reduced (30%) by 3 microM McN-A-343, and the inhibition increased (90%) with higher concentrations (100 microM). McN-A-343 also produced concentration-dependent inhibition of catecholamine secretion evoked by muscarine. A significant effect was observed at 30 microM and reached a maximum level at 300 microM. Oxotremorine, like McN-A-343 was a partial agonist on the muscarinic receptors; but unlike McN-A-343, did not block the stimulatory effects of nicotine. Although the pirenzepine data suggest that M1 receptors are responsible for the secretion of catecholamines in the rat adrenal medulla, this conclusion is not supported by the results obtained with the M1-receptor agonist, McN-A-343, which proved to be an effective blocker of muscarinic as well as nicotinic receptors.
使用哌仑西平、 McN-A-343 和氧化震颤素确定参与大鼠离体灌注肾上腺分泌儿茶酚胺的毒蕈碱受体亚型。在存在0.1微摩尔哌仑西平的情况下，毒蕈碱的浓度-分泌曲线平行右移近一个对数单位。浓度为0.5微摩尔时，右移超过两个对数单位。哌仑西平的表观解离常数约为1.12×10⁻⁸ M。用 McN-A-343（1 - 30微摩尔）灌注未引起儿茶酚胺分泌。进一步增加到非常高的浓度（100 - 1000微摩尔）仅引起适度分泌（300微摩尔时约为50纳克/5分钟，而1微摩尔毒蕈碱引起相同分泌量）。3微摩尔 McN-A-343可使尼古丁引起的分泌显著减少（30%），且随着浓度升高（100微摩尔）抑制作用增强（90%）。McN-A-343还对毒蕈碱引起的儿茶酚胺分泌产生浓度依赖性抑制。在30微摩尔时观察到显著作用，在300微摩尔时达到最大水平。氧化震颤素与McN-A-343一样是毒蕈碱受体的部分激动剂；但与McN-A-343不同的是，它不阻断尼古丁的刺激作用。尽管哌仑西平的数据表明M1受体负责大鼠肾上腺髓质中儿茶酚胺的分泌，但M1受体激动剂McN-A-343的结果并不支持这一结论，McN-A-343被证明是毒蕈碱受体以及烟碱受体的有效阻断剂。
