Effects of RS17053 on α1‐adrenoceptors in rat vas deferens and aorta

Abstract

AbstractBackgroundRS17053 is classed as an α1A‐adrenoceptor selective antagonist.ObjectivesWe have examined its profile of action at all subtypes of α1‐adrenoceptor.MethodsNoradrenaline (NA) evoked contractions of rat vas deferens involve α1D‐adrenoceptors in phasic contractions and α1A‐adrenoceptors in tonic contractions. Contractions of rat aorta to NA involve α1D‐ and α1B‐adrenoceptors.ResultsRS17053 (10−5 M) shifted NA potency and virtually abolished tonic contractions to NA, with little or limited effect on phasic contractions. The α1D‐adrenoceptor antagonist BMY7378 (3 × 10−7 M) significantly inhibited the remaining phasic component of the contractions, and the α1A‐adrenoceptor antagonist RS100329 (10−7 M) inhibited further the residual tonic contraction. Hence, RS17053 shows high selectivity for α1A‐adrenoceptors over α1D‐adrenoceptors in rat vas deferens. However, RS17053 (10−5 M) produced a large shift in the potency of NA in rat aorta, with a pKB of 6.82. Large shifts of NA potency in rat aorta involve α1B‐adrenoceptor blockade.ConclusionResults in rat vas deferens demonstrate low potency of RS17053 at α1D‐adrenoceptors, but results from rat aorta can only be explained as demonstrating α1B‐adrenoceptor antagonism by RS17053. RS17053 may be a useful pharmacological tool when reclassified as a mainly α1A‐ and to a lesser extent α1B‐adrenoceptor antagonist with little effect at α1D‐adrenoceptors.