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Pharmacological Analysis of Beta-adrenoceptor-mediated Agonism in the Guinea-pig, Isolated, Right Atrium

Overview
Journal Br J Pharmacol
Publisher Wiley
Specialty Pharmacology
Date 1985 Mar 1
PMID 2859066
Citations 9
Authors
J W Black
V P Gerskowitch
P Leff
N P Shankley
Affiliations
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Abstract

The recently developed, operational model of pharmacological agonism defines the efficacy of agonists by tau = [Ro]/KE, where [Ro] is the total functional concentration of receptors and KE is the concentration of agonist-occupied receptors for half-maximal effect. Theoretically, variations in [Ro] and KE affect tau and in turn, E/[A] curve profiles similarly. Using the beta-adrenoceptor mediated chronotropic responses of the guinea-pig isolated right atrial preparation we have investigated the consequences of experimental [Ro] and KE variation. Bromoacetylalprenolol menthane (M-75) produced displacements of isoprenaline and dichloroisoprenaline E/[A] curves consistent with [Ro] reduction. Cholera toxin produced displacements consistent with decreases in KE. The operational model provides a simple conceptual framework for the prediction and interpretation of changes in E/[A] curve profile resulting from experimental interventions at the post-receptor (KE) level as well as at the receptor ([Ro]) level.

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