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.

Current models of human prostate contractility

“…8 Human prostatic tissue also responds to the addition of ␣ 1 -adrenoceptor agonists with contractions 9 that are blocked by subtype-selective ␣ 1 -adrenoceptor antagonists. 10 Consistent with this finding is evidence that ␣ 1A ( ␣ 1c -)-adrenoceptors predominate in this tissue. 11 ␣ -Adrenoceptor-mediated contractions are also inhibited by pertussis toxin and are sensitive to (L-type) Ca 2+ channel blockers.…”

Demonstration of .ALPHA.1-adrenoceptors in human hypertrophied prostate with tritiated bunazosin.

“…bunazosin is a potent postsynaptic al-blocker with a higher selectivity than that of prazosin (13,14), [3H]-bunazosin should also be a useful ligand for binding assays (3,13,14). The al-adrenoceptors in the prostate were reported to be localized in the stroma by Chappel et al (2) and James et al (4). Our previous study (6,12) demonstrated the approximate localization of aladrenoceptors in the human prostate using [3H]-prazosin and [125I]-HEAT.…”

“…Recent research on adrenoceptors in the human prostate has mainly been performed using binding assays and in vitro receptor autoradiography, which has demonstrated that both [3H]-prazosin and [1251]_ iodo-2-[8-(4-hydroxyphenyl)-ethylaminomethyl] tetralone ([125I]-HEAT) bind specifically to the a1-adrenoceptors (2,4,10,11). We have also reported on the density and localization of a1-receptors in the hypertrophic prostate using the same ligands (6,12).…”

Beni̇gn Prostat Hi̇perplazi̇si̇'ni̇n Semptomati̇k Tedavi̇si̇nde Terazosi̇ni̇n Etki̇nli̇ği̇ Ve Güveni̇li̇rli̇ği̇ (Çi̇ft Kör Plesebo Kontrollü Çalişma)

“…Prostat dokusunda hem alfa-l reseptörlerin hemde alfa-2 reseptörlerin bulunmasına karşın düz kasların kasılmasında alfa-l reseptörlerin sorumlu olduğu, alfa-2 reseptörlerin ise özellikle nor-adrenalin salgılanmasını kontrol eden feedback mekanizmasında rol oynadığı bilinmektedir (13,14,15). Selektif alfa-l blokörlerinin kullanımı ise, prazosin ile yapılan deneylerden sonra yaygınlaşmıştır.…”