Autoradiographic Analysis of Alpha-Adrenoceptors and Muscarinic Cholinergic Receptors in the Hyperplastic Human Prostate

Abstract

Radioligand receptor binding and autoradiography were used to characterize, localize and compare alpha-1 and alpha-2 adrenoceptors and muscarinic cholinergic receptor populations in human benign prostatic hyperplastic tissue. The binding of selective alpha-1 and alpha-2 ligands, [3H]- prazosin and [3H]-UK 14,304, to homogenates of human central and peripheral prostate was saturable and of high affinity. Scatchard analysis produced an equilibrium dissociation constant (KD) of 0.51 ± 0.10 nM for alpha-1 adrenoceptors, and 2.34 ± 0.40 nM for alpha-2 adrenoceptors. The mean densities, Bmax, of alpha-1 and alpha-2 adrenoceptors identified in the human adenomatous prostate were 65.9 ± 12.9 and 36.1 ± 7.0 fmoles/mg. protein respectively.Receptor autoradiography was used to examine the distribution of muscarinic cholinergic receptors ([3H]-QNB), alpha-1 adrenoceptors ([3H]-prazosin]), and alpha-2 adrenoceptors ([3H]-rauwolscine) on consecutive sections of benign hyperplastic prostatic tissue. Although both subtypes of adrenoceptor were seen in the stromal component of the hyperplastic prostate, there was a substantial predominance of alpha-1 adrenoceptors. A densitometric computer-assisted analysis was performed on the autoradiographic slides to determine the mean ratio of specific alpha-1: alpha-2 adrenoceptors in the stromal compartment of the hyperplastic tissue. The ratio, expressed as % grain occupancy/unit area, was 3.9 ± 0.75, which is in agreement with a functional alpha-1 adrenoceptor predominance shown in previous studies. Although sparsely distributed in the stroma, a dense alpha-2 adrenoceptor population was seen in association with blood vessels, and in close proximity to the base of some of the [3H]-QNB-labelled prostatic glandular epithelial cells.These results clearly illustrate a differential localization of specific receptors to precise prostatic regions, and future correlation between function and location might enable more selective therapeutic treatment of benign prostatic hyperplasia.