A comparison of effects measured with isotonic and isometric recording: II. Concentration-effect curves for physiological antagonists

1 If one drug, B, antagonizes another, A, by producing the opposite physiol ogical effect, the antagonist concentration-effect curves should be affecte d by the recording system, which limits the range of agonist responses. 2 With pieces of isolated guinea-pig ileum taken from adjacent parts of the same animal, one recorded isotonically, the other isometrically with the s ame load, the isotonic IC50 values for (-)isoprenaline opposing carbachol o r histamine were lower than the isometric values (P <0.01) but there was a significant correlation between them (P <0.01): the isotonic curves were st eeper (P <0.01) and there were wider shifts in IC50 before increasing the a gonist reduced the maximum relaxation. 3 In similar experiments with pieces of rat uterus in oestrus from the same animal, the concentration-effect curves for carbachol opposed by increasin g concentrations of (-)isoprenaline or (-)adrenaline had slightly lower EC5 0 values with isometric recording but there was a significant correlation ( P <0.01) with isotonic values. The antagonist effect (ratio of the EC50 rel ative to that for the control) was higher with isotonic recording (P <0.01 for ( -)isoprenaline, P <0.025 for (-)adrenaline) and all (27) curves were steeper than the corresponding isometric curve (P <0.001). 4 The influence of the method of recording on the results is expected from the narrower operational window and smaller upper limit to relaxation with isotonic recording, 5 A way of obtaining measurements of IC50 against a standard agonist effect is suggested in an Appendix.