α1L-adrenoceptors mediate contraction of human erectile tissue

Abstract

α₁-adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly α_1A-adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the α_1L-adrenoceptor. Functional experiments using subtype selective agonists and antagonists, along with radioligand ([³H]tamsulosin) binding assays, were used to determine the α₁-adrenoceptor population. A61603, a α_1A-adrenoceptor agonist, was a full agonist with a potency 21-fold greater than that of noradrenaline. The α_1A- and α_1D-adrenoceptor antagonist tamsulosin antagonized noradrenaline responses with high affinity (pK_D = 9.7 ± 0.3), whilst BMY7378 (100 nM) (α_1D-adrenoceptor antagonist) failed to antagonize responses. In contrast, relatively low affinity estimates were obtained for both prazosin (pK_D = 8.2 ± 0.1) and RS17053 (pK_D = 6.9 ± 0.2), antagonists which discriminate between the α_1A- and α_1L-adrenoceptors. [³H]Tamsulosin bound with high affinity to the receptors of human erectile tissue (pK_D = 10.3 ± 0.1) with a receptor density of 28.1 ± 1.4 fmol mg^-1 protein. Prazosin displacement of [³H]tamsulosin binding revealed a single homogenous population of binding sites with a relatively low affinity for prazosin (pK_i = 8.9). Taken together these data confirm that the receptor mediating contraction in human erectile tissue has the pharmacological properties of the α_1L-adrenoceptor.

Keywords: Erectile tissue; Prazosin; Tamsulosin; α(1)-adrenoceptor subtypes; α(1L)-adrenoceptor.