Abstract
1. The interaction of isoxuprine and nylidrin with α1- and β2-adrenoreceptors in rat vas deferens was examined using radioligand binding assays and physiological studies in vitro. 2. Isoxuprine and nylidrin have a greater affinity for binding to α1 (isoxuprine K(D) = 59 ± 15 nM; nylidrin K(D) = 41 ± 3 nM) than β2-(isoxuprine K(D) = 3,900 ± 500 nM; nylidrin K(D) = 900 ± 50 nM) adrenoreceptors in rat vas deferens. 3. Vas deferens from rats pretreated for 16-24 h with reserpine (3 mg/kg i.p.) were exposed to 10 μM phenoxybenzamine for 15 min to inactivate α-adrenoreceptors. Under these conditions high concentrations of both isoxuprine and nylidrin relaxed vas deferens contracted with 55 mM K+, however the relaxation was not blocked by the β-adrenoreceptor antagonist propranolol (10 μM). 4. Both isoxuprine and nylidrin were potent competitive antagonists of α1-adrenoreceptor mediated contraction of vas deferens. pA2 values for isoxuprine (6.9 ± .05) and nylidrin (7.1 ± .08) agreed well with K(D) values for binding to α1-adrenoreceptors in vas deferens. 5. The greater potency of isoxuprine and nylidrin in inhibiting α1-adrenoreceptors than binding to β2-adrenoreceptors or causing nonspecific relaxation suggest that α-adrenoreceptor antagonist actions of these drugs may be important in their ability to inhibit smooth muscle tone.