Barlow R B, Bond S M, Grant C, McQueen D S, Yaqoob Z
Department of Neuroscience, 1 George Square, Edinburgh EH8 9JZ, Scotland, UK.
Br J Pharmacol. 2001 Aug;133(7):1081-6. doi: 10.1038/sj.bjp.0704168.
Concentration-effect curves were obtained with carbachol tested on isolated preparations of guinea-pig ileum taken from adjacent sites in the same animal, one recorded isotonically, the other isometrically: similar experiments were made with histamine as agonist and with carbachol on rat uterus (in oestrus). The position and steepness of the curves was expressed as the values of [EC(50)] and the exponent, P: with carbachol or histamine on guinea-pig ileum the curves were significantly steeper with isotonic recording (P<0.02, sign test) and displaced towards lower concentrations (P<0.005) but there were significant correlations (P<0.05) between values obtained with tissues from the same animal. The curves for carbachol on the rat uterus were very steep: with isotonic recording the exponent (often eight or more) was consistently higher than with isometric (P<0.001): there was no significant displacement but there was a significant correlation (P<0.05) between values of [EC(50)] obtained with tissues from the same animal. Although the results obtained by the two methods are different, they are correlated. These effects are to be expected because with isotonic recording there can be no change in length until the tension exceeds the load and the tissue bulk sets an upper limit to shortening: the range within which an effect can be measured (the "operational window") is smaller. The observed effects on [EC(50)] and P have been reproduced with theoretical data.
使用卡巴胆碱对取自同一只动物相邻部位的豚鼠回肠离体标本进行测试,获得浓度-效应曲线,其中一条以等张方式记录,另一条以等长方式记录;以组胺作为激动剂对豚鼠回肠进行了类似实验,并用卡巴胆碱对大鼠子宫(处于发情期)进行了类似实验。曲线的位置和斜率以[EC(50)]值和指数P表示:用卡巴胆碱或组胺作用于豚鼠回肠时,等张记录的曲线明显更陡(P<0.02,符号检验),且向较低浓度方向移动(P<0.005),但同一动物组织获得的值之间存在显著相关性(P<0.05)。卡巴胆碱作用于大鼠子宫的曲线非常陡峭:等张记录时指数(通常为8或更高)始终高于等长记录(P<0.001);没有明显的位移,但同一动物组织获得的[EC(50)]值之间存在显著相关性(P<0.05)。虽然两种方法得到的结果不同,但它们是相关的。这些效应是可以预期的,因为在等张记录中,直到张力超过负荷,长度才会改变,并且组织体积为缩短设定了上限:可测量效应的范围(“操作窗口”)较小。观察到的对[EC(50)]和P的影响已通过理论数据重现。