α1L-adrenoceptors mediate contraction of human erectile tissue

Publication date: Available online 9 August 2018Source: Journal of Pharmacological SciencesAuthor(s): Beverley J. Davis, Christopher R. Chapple, Donna J. Sellers, Alistair L. Naylor, David Sillar, Alistair Campbell, Russ Chess-WilliamsAbstractα1-adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly α1A-adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the α1L-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 α1A-adrenoceptor agonist, was a full agonist with a potency 21-fold greater than that of noradrenaline. The α1A- and α1D-adrenoceptor antagonist tamsulosin antagonized noradrenaline responses with high affinity (pKD=9.7±0.3), whilst BMY7378 (100nM) (α1D-adrenoceptor antagonist) failed to antagonize responses. In contrast, relatively low affinity estimates were obtained for both prazosin (pKD=8.2±0.1) and RS17053 (pKD=6.9±0.2), antagonists which discriminate between the α1A- and α1L-adrenoceptors. [3H]Tamsulosin bound with high affinity to the receptors of human erectile tissue (pKD=10.3±0.1) with a receptor density of 28.1±1.4 fmoles mg-1 protein. Prazosin displacement of [3H]tamsulosin binding revealed a single homogenous populatio...
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research