三氟拉嗪刺激培养的鸡肌管中乙酰胆碱受体的合成。

Trifluoperazine stimulates acetylcholine receptor synthesis in cultured chick myotubes.

作者信息

Schneider M, Shieh B H, Pezzementi L, Schmidt J

出版信息

J Neurochem. 1984 May;42(5):1395-401. doi: 10.1111/j.1471-4159.1984.tb02800.x.

DOI:10.1111/j.1471-4159.1984.tb02800.x

Abstract

Acetylcholine receptor appearance rate in the presence of the phenothiazines trifluoperazine and chlorpromazine was measured in cultured embryonic chick myotubes by means of 125I-alpha-bungarotoxin. At drug concentrations of 5 to 10 X 10(-6) M, receptor appearance rate was significantly enhanced while receptor half-life, cellular protein, net protein synthesis rate, and acetylcholinesterase levels were not similarly affected. The sulfoxide derivatives were without effect. At concentrations of 3 X 10(-5) M and above, both trifluoperazine and chlorpromazine caused myotube contracture and cell loss. Drug combination experiments revealed that receptor stimulation caused by phenothiazines is overcome by low concentrations of veratridine and ryanodine, but not by membrane depolarization with 20 mM KCl. These results lend support to the role of calcium as an intracellular messenger in acetylcholine receptor synthesis regulation, but are difficult to reconcile with the notion that cytosolic calmodulin serves as the calcium receptor in this signaling pathway. Since the trifluoperazine effect resembles that caused by the calcium antagonist D-600, phenothiazines may stimulate receptor synthesis by blocking a voltage-gated calcium channel.

摘要

通过使用¹²⁵I-α-银环蛇毒素，在培养的胚胎鸡肌管中测量了在存在吩噻嗪类药物三氟拉嗪和氯丙嗪的情况下乙酰胆碱受体的出现率。在药物浓度为5至10×10⁻⁶ M时，受体出现率显著提高，而受体半衰期、细胞蛋白、净蛋白合成率和乙酰胆碱酯酶水平未受到类似影响。亚砜衍生物没有作用。在浓度为3×10⁻⁵ M及以上时，三氟拉嗪和氯丙嗪均导致肌管挛缩和细胞损失。药物联合实验表明，吩噻嗪类药物引起的受体刺激可被低浓度的藜芦定和雷诺丁克服，但不能被20 mM KCl引起的膜去极化克服。这些结果支持钙作为乙酰胆碱受体合成调节中的细胞内信使的作用，但难以与胞质钙调蛋白作为该信号通路中的钙受体这一概念相协调。由于三氟拉嗪的作用类似于钙拮抗剂D-600引起的作用，吩噻嗪类药物可能通过阻断电压门控钙通道来刺激受体合成。