Effects of RS17053 on ₁-adrenoceptors in rat vas deferens and aorta

Background: RS17053 is classed as an a(1A)-adrenoceptor selective antagonist.Objectives: We have examined its profile of action at all subtypes of a(1)-adrenoceptor.Methods: Noradrenaline (NA) evoked contractions of rat vas deferens involve a(1D)-adrenoceptors in phasic contractions and a(1A)-adrenoceptors in tonic contractions. Contractions of rat aorta to NA involve a(1D)- and a(1B)-adrenoceptors.Results: RS17053 (10(-5) M) shifted NA potency and virtually abolished tonic contractions to NA, with little or limited effect on phasic contractions. The a(1D)-adrenoceptor antagonist BMY7378 (3 x 10(-7) M) significantly inhibited the remaining phasic component of the contractions, and the a(1A)-adrenoceptor antagonist RS100329 (10(-7) M) inhibited further the residual tonic contraction. Hence, RS17053 shows high selectivity for a(1A)-adrenoceptors over a(1D)-adrenoceptors in rat vas deferens. However, RS17053 (10(-5) M) produced a large shift in the potency of NA in rat aorta, with a pK(B) of 6.82. Large shifts of NA potency in rat aorta involve a(1B)-adrenoceptor blockade.Conclusion: Results in rat vas deferens demonstrate low potency of RS17053 at a(1D)-adrenoceptors, but results from rat aorta can only be explained as demonstrating a(1B)-adrenoceptor antagonism by RS17053. RS17053 may be a useful pharmacological tool when reclassified as a mainly a(1A)- and to a lesser extent a(1B)-adrenoceptor antagonist with little effect at a(1D)-adrenoceptors.