Quantitative autoradiography of α1 adrenoceptors with [3H]tamsulosin in human hypertrophied prostate using computerized image analysis

Abstract

Fourteen specimens of human hypertrophied prostate were evaluated for the distribution of alpha 1 adrenoceptors using autoradiography with a computerized image analysis system. The hypertrophied prostatic specimens, obtained at open prostatectomy, were dissected vertically to the urethra, and sectioned at 10 microns. They were immersed in 1 nM of specific alpha 1 ligand, [3H]tamsulosin chloride ([3H]tamsulosin) and exposed to autoradiographic film. The images were analysed by a computerized image analysis system. The total binding of [3H]tamsulosin in the whole section (n = 14) was 0.82 +/- 0.21 (mean +/- SE) nCi mg-1. The autographic data were correlated with data obtained in a membrane-binding assay. The prostatic tissue studied was divided into urethral, glandular and stromal zones, the latter two zones being further divided into the inner and outer areas. The total binding of [3H]tamsulosin in the urethral zone (n = 7) was 0.65 +/- 0.32 nCi mg-1. The glandular zone contained significantly more abundant alpha 1 adrenoceptors than the stromal zone and their densities (glandular vs stromal) were 1.15 +/- 0.19 nCi mg-1 (n = 14) vs 0.72 +/- 0.15 nCi mg-1 (n = 14), respectively (p < 0.05). The data from the whole section were not affected by prostatic weight. This method described enabled the distribution of the receptors in different sites to be evaluated both morphologically and quantitatively.

Mode of action of α1‐adrenoreceptor antagonists in the treatment of lower urinary tract symptoms

“…Stromal elements [15] and the density of stromal α 1 ‐ARs [16–18] are increased in BPH. α 1 ‐ARs occur in the glandular epithelium [19] and seem to be of the α 1B ‐subtype [20]. Although there may be regional differences in the binding to and functional properties of the prostatic α 1 ‐ARs [21], there is no evidence of clinically significant regional differences in the contractile responses to α 1 ‐AR agonists [22].…”

Evaluation of histological structure and its effect on the distribution of α1‐adrenoceptors in human benign prostatic hyperplasia

“…To estimate the density of α1‐adrenoceptors on smooth muscle, the binding data described previously [ 9] were re‐evaluated according to eqn (1). The mean (sd) density per smooth muscle area in the hyperplastic acinar nodule was 6.04 (1.89) nCi/mg while that in the surrounding stroma was 1.17 (0.32) nCi/mg ( P <0.05).…”

“…Franks [ 8] described five types of hyperplastic nodule and referred to the septal structure of the interstitium surrounding the lobules of hyperplastic nodules. We previously investigated the regional differences in α1‐adrenoceptors using computerized image analysis with macroautoradiography [ 9]. The aim of the present study was to further evaluate the regional differences in α1‐adrenoceptor density as related to smooth muscle distribution according to the histological structure suggested by Franks [ 8].…”

Current status of research on prostate‐selective α1‐antagonists

“…Nonspecific α‐adrenoceptor binding was quantified using phentolamine; this showed that the level of binding to α‐adrenoceptors other than α 1A ‐adrenoceptors in the prostate was low. Using this technique, tamsulosin‐binding sites and therefore α 1A ‐adrenoceptors were shown to occur mainly in the hyperplastic nodular portion of the gland [ 6].…”