Hedtke J L, Shideman F E, Goldberg N D
J Pharmacol Exp Ther. 1976 Apr;197(1):27-37.
The characteristics of the positive inotropic effect of different preparations of cholera toxin on the isolated 4-day-old embryonic chick heart were investigated. Crude (CCT) as well as partially purified and purified (PCT)preparations of cholera toxin were shown to have positive inotropic activity. Contractility was increased within 1 minute and reached a maximum at approximately 40 minutes after exposure to toxin. Activities of all three toxin preparations were abolished by heating, their effects were prevented by addition of antitoxin, but nort propranolol, before exposure of the heart to toxin. The positive inotropic effect of PCT was not reversed by washing, but was reversed by subsequent addition of antitoxin. The effects of CCT were reversed by insulin. Effects of both CCT and PCT were potentiated by theophylline, and both toxin preparations elevated tissue levels of cyclic adenosine 3',5'-monophosphate. A filtrate of CCT (MW is less than 30,000) exhibited similar cardiostimulant activity but displayed certain differences from the other toxin preparations. The filtrate was heat stable, and its effects were blocked by pretreatment with propranolol but not by antitoxin. The filtrate of CCT, unlike the toxin-containing preparations, did not stimulate intestinal fluid secretion in the dog.
研究了霍乱毒素不同制剂对离体4日龄鸡胚心脏正性肌力作用的特点。结果显示,霍乱毒素的粗制品(CCT)以及部分纯化和纯化制品(PCT)均具有正性肌力活性。暴露于毒素后1分钟内收缩力增强,约40分钟时达到最大值。所有三种毒素制剂的活性经加热后均被消除,在心脏暴露于毒素之前加入抗毒素可阻止其作用,但心得安无效。PCT的正性肌力作用经冲洗后不能逆转,但随后加入抗毒素可逆转。CCT的作用可被胰岛素逆转。茶碱可增强CCT和PCT的作用,两种毒素制剂均可提高组织中环磷酸腺苷(cAMP)的水平。CCT的一种滤液(分子量小于30,000)表现出类似的心脏刺激活性,但与其他毒素制剂存在某些差异。该滤液对热稳定,其作用可被心得安预处理阻断,但不能被抗毒素阻断。与含毒素制剂不同,CCT的滤液不会刺激犬的肠液分泌。