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Experimental testing of Mackay's model for functional antagonism in the isolated costo‐uterus of the rat
Author(s) -
Henry Peter J.,
Lulich Karmelo M.,
Paterson James W.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb09443.x
Subject(s) - antagonism , carbachol , phenoxybenzamine , antagonist , schild regression , agonist , fenoterol , chemistry , oxotremorine , medicine , uterus , partial agonist , endocrinology , receptor , pharmacology , stimulation , biology , biochemistry , asthma
1 Several key predictions of a recently developed model for functional antagonism (Mackay, 1981) were experimentally tested using the rat isolated costo‐uterine preparation. 2 In the presence of the functional antagonist fenoterol (Fen), the functional affinity constants ( K A F ) for carbachol and oxotremorine (Oxo) were respectively 9.9 and 3.4 fold greater than their corresponding affinity constants ( K A ). According to Mackay's model for functional antagonism, the higher K A F / K A ratio for carbachol indicates that this cholinoceptor agonist has a greater efficacy than Oxo. This was confirmed by using conventional pharmacological methods. 3 As predicted from the model of functional antagonism, the plot of K A F / K A ‐ 1 against the fraction of cholinoceptors not irreversibly blocked by phenoxybenzamine (Pbz) was linear for both carbachol and Oxo and the lines of best fit crossed the axes at a point not significantly different from the origin. 4 The value of 4.6 for the relative efficacy of carbachol to Oxo estimated from functional antagonism studies was comparable to the value of 5.6 calculated using the method of irreversible antagonism proposed by Furchgott (1966).