Characterisation of Human Prostatic Adrenoceptors using Pharmacology Receptor Binding and Localisation

Abstract

Benign prostatic enlargement is a common cause of bladder outlet obstruction. Recent work has demonstrated the important role played by the sympathetic nervous system in the control of prostatic muscle tone. Although isometric muscle strip studies and clinical trials have highlighted the influence of alpha-1 adrenoceptors, radioisotope ligand binding studies have demonstrated a relatively increased density of alpha-2 adrenoceptors in the muscle within prostatic tissue, the significance of which is as yet unexplained. Forty patients entered a study using pharmacological muscle strip experiments, radioligand binding assays and receptor autoradiography. Pharmacological data from these studies confirmed that contraction of prostatic muscle is mediated predominantly by alpha-1 adrenoceptor stimulation, with no evidence of significant alpha-2 adrenoceptor or cholinergic mediated effects. Radioligand binding studies confirmed that there is a higher concentration of alpha-1 binding sites as contrasted to alpha-2 within normal prostate, but that this relationship approaches equity in adenomatous prostate. Autoradiographic localisation demonstrated that alpha-1 adrenoceptor binding is predominant within prostatic stroma with only a small component of alpha-2 adrenoceptors in this compartment. This comprehensive study supports the suggestion that prostatic muscular contraction is controlled by the influence of the sympathetic nervous system acting via alpha-1 adrenoceptors. These findings support the therapeutic use of specific alpha-1 adrenoceptor blockade in the management of benign prostatic hyperplasia.