Autoradiographic localisation and contractile properties of prostatic endothelin receptors in patients with bladder outlet obstruction

Objectives: Previous studies have used endothelin (ET) receptor agonists an d antagonists to localise ET receptor subtypes in prostatic tissue. We have utilised high affinity ETA ([(125I)]PD151242) and ETB ([I-125]BQ3020) rece ptor-specific radioligands to determine the density and distribution of ET receptor subtypes in prostatic tissues obtained from patients with symptoma tic benign prostatic hyperplasia (BPH). The contractile properties of the E T receptor subtypes as well as the effect of ET-1 on alpha (1)-adrenergic r eceptor-mediated prostatic smooth muscle contraction were assessed. Patients and Methods: Saturation binding and quantitative autoradiographic studies were performed using specific radioligands for ETA and ETB receptor s on prostate sections obtained from patients with bladder outflow obstruct ion secondary to BPH. In vitro isometric tension studies were carried out t o characterise the ET receptor subtypes in prostatic smooth muscle strips f rom the same group of patients. In addition, the effect of ET-1 on alpha (1 )-adrenergic receptor-induced prostatic smooth muscle contraction was also investigated. Results: There were dense ETA and ETB receptor-binding sites in the prostat ic stroma. ETA receptor-binding sites were also prominent on the prostatic epithelium. ET-1 and sarafotoxin 6 c (ETB receptor agonist) elicited prosta tic smooth muscle contraction (-log EC50 8.31+/-0.15 and 8.22+/-0.22 M, res pectively). Both BQ123 (ETA antagonist) and BQ788 (ETB antagonist) signific antly inhibited ET-1- and S6c-mediated prostatic smooth muscle contractile responses, respectively. ET-1 at sub-threshold concentrations significantly enhanced alpha (1)-adrenergic receptor-mediated prostatic smooth muscle co ntractile responses. Conclusions: ETA receptor-binding sites are prominent in both prostatic str oma and epithelium, whereas ETB receptor-binding sites were predominantly s een in the prostatic stroma in symptomatic BPH. Both ETA and ETB receptors mediate prostatic smooth muscle contraction. ET-1 enhances alpha (1)-adrene rgic receptor-mediated contractile responses, suggesting that ET may play a pathophysiological role in bladder outlet obstruction associated with BPH. Copyright (C) 2001 S. Karger AG, Basel.