Abstract
The interaction of agonists and antagonists with alpha sub(1)-adrenergic receptors in rat vas deferens was examined using radioligand binding assays and contractility measurements. super(125)I-Labeled BE 2254 ( super(125)IBE) was found to bind rapidly and reversibly to a single class of high-affinity binding sites in homogenates of rat vas deferens. The k sub(1) for association was 3.8 x 10 super(7) 1/mole-sec, the k sub(-1) for dissociation was 2.3 x 10 super(-3) sec super(-1), and the K sub(D) was 105 pM. The order of potency for antagonists inhibiting super(125)IBE binding was prazosin > indoramin > phentolamine > yohimbine. Norepinephrine, phenylephrine, and other alpha-adrenergic agonists produced dose-dependent contractions of whole vas deferens in vitro. This contractile response was competitively inhibited by alpha-adrenergic blocking drugs with the same potency order observed for inhibition of specific super(125)IBE binding. The results suggest that rat vas deferens contains a homogeneous population of alpha sub(1)-adrenergic receptors mediating the contractile response to norepinephrine, that these receptors can be directly labeled with super(125)IBE, and that there may be a nonlinear relationship between agonist occupancy of alpha sub(1)-adrenergic receptors and the functional response of this tissue.