A comparison of effects measured with isotonic and isometric recording: I. Concentration-effect curves for agonists

1 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). 2 The position and steepness of the curves was expressed as the values of [EC50] 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. 3 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 [EC50] obtained with tissues from the same animal. 4 Although the results obtained by the two methods are different, they are correlated. 5 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 [EC50] and P have been reproduced with theoretical data.