The effect of preload on the dissociation constant of phentolamine in isolated rabbit thoracic aorta.
The affinity of phentolamine for the alpha-adrenergic receptor of isolated rabbit thoracic aorta was determined under two different preload conditions. In one condition, strips or rings or aorta were preloaded with a 1/4 g weight; in the other condition, with a 10 g weight. To measure affinity, dose-response curves were first obtained for agonist alone and then for agonist in the presence of various concentrations of phentolamine, a reversible alpha-adrenergic antagonist. From these curves, equieffective agonist concentrations were selected and Schild plots constructed to determine the dissociation constant (1/affinity). It was found that values of the dissociation constant, KB, for phentolamine were independent of the agonist used (norepinephrine or phenylephrine) to obtain the dose-response curves. KB was, however, a function of preload conditions. In all cases, IB at 1/4 g was greater than KB at 10 g preload. The magnitude of this difference in affinity with preload though, was less then previously obtained for agonists in the same preparation. The implications of this finding are discussed in terms of the effect of preload on receptor conformation and possible differences between agonist and antagonist binding.
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D004347:Drug Interactions; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009638:Norepinephrine; D010646:Phentolamine