A fundamental temperature-dependent difference between beta-adrenoceptor agonists and antagonists.

R G Chess-Williams; K J Broadley; C Duncan

doi:10.1016/0024-3205(84)90074-2

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A fundamental temperature-dependent difference between beta-adrenoceptor agonists and antagonists.

R G Chess-Williams·K J Broadley·C Duncan

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Abstract

Positive inotropic and chronotropic responses of guinea-pig isolated left and right atria to sympathomimetic amines were examined at bath temperatures of 38, 30 or 25 degrees C. The concentration-response curves to isoproterenol and orciprenaline were displaced to the left by cooling, indicating hypothermia-induced supersensitivity. The affinities of isoproterenol and orciprenaline were determined as their dissociation constants (pKA) from antagonism of their responses by either the functional antagonist carbachol or Ro 03-7894 which is reported to be an irreversible beta-adrenoceptor antagonist. By both methods of calculation, the affinities of isoproterenol and orciprenaline for the beta-adrenoceptors mediating inotropic and chronotropic responses were increased by lowering the temperature. In contrast, the affinity of practolol, measured as the pA2 for competitive antagonism of the isoproterenol- and orciprenaline-induced inotropic and chronotropic responses, did not increase with cooling. Thus hypothermia-induced supersensitivity is associated with an increase in agonist affinity only, which indicates a fundamental temperature-dependent difference between agonist and antagonist interactions with the beta-adrenoceptor.

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Animals Dose-Response Relationship, Drug Female Guinea Pigs Heart Rate Isoproterenol Male Metaproterenol Myocardial Contraction Receptors, Adrenergic, beta Stimulation, Chemical Temperature Time Factors Journal Article Research Support, Non-U.S. Gov't

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R G Chess-Williams, K J Broadley, C Duncan. 1984-09-03. A fundamental temperature-dependent difference between beta-adrenoceptor agonists and antagonists.. https://doi.org/10.1016/0024-3205(84)90074-2

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