Experimental testing of Mackay's model for functional antagonism in the isolated costo‐uterus of the rat

Peter J. Henry, Karmelo M. Lulich, James W. Paterson

    Research output: Contribution to journalArticle

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    Abstract

    Several key predictions of a recently developed model for functional antagonism (Mackay, 1981) were experimentally tested using the rat isolated costo‐uterine preparation. In the presence of the functional antagonist fenoterol (Fen), the functional affinity constants (KAF) for carbachol and oxotremorine (Oxo) were respectively 9.9 and 3.4 fold greater than their corresponding affinity constants (KA). According to Mackay's model for functional antagonism, the higher KAF/KA ratio for carbachol indicates that this cholinoceptor agonist has a greater efficacy than Oxo. This was confirmed by using conventional pharmacological methods. As predicted from the model of functional antagonism, the plot of KAF/KA ‐ 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. 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). 1985 British Pharmacological Society

    Original languageEnglish
    Pages (from-to)131-139
    Number of pages9
    JournalBritish Journal of Pharmacology
    Volume86
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 1985

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    Oxotremorine
    Carbachol
    Cholinergic Receptors
    Fenoterol
    Phenoxybenzamine
    Pharmacology

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    abstract = "Several key predictions of a recently developed model for functional antagonism (Mackay, 1981) were experimentally tested using the rat isolated costo‐uterine preparation. In the presence of the functional antagonist fenoterol (Fen), the functional affinity constants (KAF) for carbachol and oxotremorine (Oxo) were respectively 9.9 and 3.4 fold greater than their corresponding affinity constants (KA). According to Mackay's model for functional antagonism, the higher KAF/KA ratio for carbachol indicates that this cholinoceptor agonist has a greater efficacy than Oxo. This was confirmed by using conventional pharmacological methods. As predicted from the model of functional antagonism, the plot of KAF/KA ‐ 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. 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). 1985 British Pharmacological Society",
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    Experimental testing of Mackay's model for functional antagonism in the isolated costo‐uterus of the rat. / Henry, Peter J.; Lulich, Karmelo M.; Paterson, James W.

    In: British Journal of Pharmacology, Vol. 86, No. 1, 01.01.1985, p. 131-139.

    Research output: Contribution to journalArticle

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