A test of the null equation for functional antagonism.

Abstract

1 The quantitative model for functional antagonism and synergism has been tested by studying its ability to fit data obtained from the functional antagonism of (-)-isoprenaline by muscarinic agonists on guinea-pig isolated atria. 2 The general form of the null equation has been shown to fit the experimental curves satisfactorily. 3 Functional interaction between (-)-isoprenaline and muscarinic agonists on atria has been shown to be type I although there does seem to be a discrepancy between values of the functional affinity constants, KA1F and KA2F, estimated in two different ways. 4 The affinity constants, KA, of the muscarinic agonists for their receptors have been estimated by use of the selective irreversible antagonist propylbenzilylcholine mustard. The discrepancy between KAF (i.e. both KA1F and KA2F) and KA is small for pentyltrimethylammonium which is an agonist of low intrinsic efficacy. By contrast the discrepancy between KAF and KA is much greater for methylfurmethide and oxotremorine both of which have much higher intrinsic efficacies. These results are as predicted by the model. 5 It is suggested that the discrepancy between KA1F and KA2F may be due to the limited ability of the equation l/S omega = aI + bI/S alpha to describe quantitatively the relation between sequential stimuli. However, it is concluded that this complication need not interfere with the use of the model to study mechanisms and possible sites of functional interaction.