Akasu T, Kojima M, Koketsu K
Br J Pharmacol. 1983 Sep;80(1):123-31. doi: 10.1111/j.1476-5381.1983.tb11057.x.
The effect of substance P on the sensitivity of nicotinic acetylcholine (ACh) receptors of bullfrog sympathetic ganglion cells and frog skeletal muscle endplate was examined electrophysiologically. The amplitude of ACh-induced postsynaptic potential (ACh potential) and current (ACh current) were reversibly and dose-dependently reduced by substance P at low concentrations (0.42-42 microM). The mean amplitude of the miniature endplate potential (m.e.p.p.) was also reduced by substance P (4.2 microM). Substance P (4.2 microM) shifted the S-shaped dose-response curve of the ACh current downward. A Lineweaver-Burk plot constructed from the dose-response curve revealed that substance P depressed the maximum response (Vmax) without changing the apparent affinity (Km) of ACh for the receptor. Substance P (0.42-42 microM) did not alter the reversal potential of the ACh current of the endplate. The half-decay time of endplate current (e.p.c.) and its voltage-dependency were not altered by substance P in these concentrations. The depression of the ACh current by substance P may not be due to a blockade of the opened channel which has been activated by the preceding combination of ACh with the receptor. These results suggest that substance P suppresses the sensitivity of nicotinic ACh-receptors of the sympathetic ganglion cell and skeletal muscle endplate, acting on a certain allosteric site but not the recognition site of ACh in the receptor-ionic channel complex.
用电生理学方法研究了P物质对牛蛙交感神经节细胞烟碱型乙酰胆碱（ACh）受体及蛙骨骼肌终板敏感性的影响。在低浓度（0.42 - 42微摩尔）时，P物质可使ACh诱导的突触后电位（ACh电位）和电流（ACh电流）的幅度呈剂量依赖性可逆性降低。微小终板电位（m.e.p.p.）的平均幅度也被P物质（4.2微摩尔）降低。P物质（4.2微摩尔）使ACh电流的S形剂量反应曲线向下移位。根据剂量反应曲线构建的Lineweaver - Burk图显示，P物质降低了最大反应（Vmax），而不改变ACh对受体的表观亲和力（Km）。P物质（0.42 - 42微摩尔）未改变终板ACh电流的反转电位。在这些浓度下，P物质未改变终板电流（e.p.c.）的半衰期及其电压依赖性。P物质对ACh电流的抑制作用可能不是由于阻断了先前ACh与受体结合所激活的开放通道。这些结果表明，P物质通过作用于受体 - 离子通道复合物中ACh的某个变构位点而非识别位点，抑制交感神经节细胞和骨骼肌终板烟碱型ACh受体的敏感性。
