α-adrenoceptors mediate contraction of human erectile tissue.

α-adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly α-adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the α-adrenoceptor. Functional experiments using subtype selective agonists and antagonists, along with radioligand ([H]tamsulosin) binding assays, were used to determine the α-adrenoceptor population. A61603, a α-adrenoceptor agonist, was a full agonist with a potency 21-fold greater than that of noradrenaline. The α- and α-adrenoceptor antagonist tamsulosin antagonized noradrenaline responses with high affinity (pK = 9.7 ± 0.3), whilst BMY7378 (100 nM) (α-adrenoceptor antagonist) failed to antagonize responses. In contrast, relatively low affinity estimates were obtained for both prazosin (pK = 8.2 ± 0.1) and RS17053 (pK = 6.9 ± 0.2), antagonists which discriminate between the α- and α-adrenoceptors. [H]Tamsulosin bound with high affinity to the receptors of human erectile tissue (pK = 10.3 ± 0.1) with a receptor density of 28.1 ± 1.4 fmol mg protein. Prazosin displacement of [H]tamsulosin binding revealed a single homogenous population of binding sites with a relatively low affinity for prazosin (pK = 8.9). Taken together these data confirm that the receptor mediating contraction in human erectile tissue has the pharmacological properties of the α-adrenoceptor.