Pharmacological analysis of beta-adrenoceptor-mediated agonism in the guinea-pig, isolated, right atrium.
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.
Black
J W
JW
Gerskowitch
V P
VP
Leff
P
P
Shankley
N P
NP
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000526:Alprenolol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; C045331:bromoacetylalprenololmenthane; D000526:Alprenolol; D002772:Cholera Toxin; D007545:Isoproterenol