Sympathectomy reveals α 1A ‐ and α 1D ‐adrenoceptor components to contractions to noradrenaline in rat vas deferens

We have previously demonstrated that contractions of rat vas deferens to exogenous noradrenaline involve predominantly α 1A ‐adrenoceptors, but that contractions to endogenous noradrenaline involve predominantly α 1D ‐adrenoceptors. In this study, we have examined the effects of sympathectomy on the subtypes of α 1 ‐adrenoceptor in rat vas deferens in radioligand binding and functional studies. In vehicle‐treated tissues, antagonist displacement of [ 3 H]prazosin binding to α 1 ‐adrenoceptors was consistent with a single population of α 1 ‐adrenoceptors. Binding affinities for a range of α 1 ‐adrenoceptor antagonists were expressed as p K i values and correlated with known affinities for α 1 ‐adrenoceptor subtypes. The correlation was significant only with α 1A ‐adrenoceptors. In tissues from rats sympathectomised with 6‐hydroxy‐dopamine (2 × 100 mg kg −1 i.p.), binding affinity for the α 1D ‐adrenoceptor antagonist BMY 7378 fitted best with a two‐site model. In functional studies, the potency of noradrenaline at producing total (phasic plus tonic) but not tonic contractions was increased in tissues from sympathectomised rats. Results obtained from sympathectomised rats suggest that phasic contractions are mainly α 1D ‐adrenoceptor mediated, whereas tonic contractions are mainly α 1A ‐adrenoceptor mediated, based on the effects of BMY 7378 and the α 1A ‐adrenoceptor antagonist RS 100329. It is concluded that the predominant α 1 ‐adrenoceptor in vehicle‐treated rat vas deferens is the α 1A ‐adrenoceptor, both in terms of ligand binding and contractions to exogenous agonists. The α 1D ‐adrenoceptor is only detectable by ligand binding following chemical sympathectomy, but is involved in noradrenaline‐evoked contractions, particularly phasic contractions, of rat vas deferens.British Journal of Pharmacology (2004) 143 , 745–752. doi: 10.1038/sj.bjp.0705987