The role of alpha_1-adrenoceptor for the prostatic interstitium and glandular epithelium in human prostate

A)人前列腺尿道中α _1-肾上腺素受体亚型的鉴定1。为了鉴定人前列腺尿道中的α _1-肾上腺素能受体亚型，我们比较了各种α _1-肾上腺素能受体激动剂和拮抗剂抑制[^3H]坦舒洛辛与人前列腺尿道膜结合的效力，以及它们抑制[^<125>]HEAT与克隆人α _<1a>、α _<1b>和α _<1d>结合的效力。α <1A> α选择性拮抗剂5-甲基脲地尔和尼古地平对克隆的α <1A>和尿道α _1-肾上腺素受体的亲和力均高于对克隆的α _<1b>和α _<1d>-肾上腺素受体的亲和力。alpha_<1A>-选择性激动剂对克隆的alpha_<1A>亚型和尿道alpha_1-肾上腺素受体也表现出高亲和力。Prazosin对人前列腺尿道中α _1-肾上腺素受体的亲和力较低。人前列腺尿道α _1-肾上腺素受体激动剂与蚂蚁受体激动剂的亲和性比较表明，人尿道α _1-与克隆的α _<1a>-肾上腺素受体亲和性密切相关。然而，哌唑嗪不符合这种模式。这些发现表明，人类尿道中主要的α _1-肾上腺素受体是α _<1A>亚型，而α _<1L>亚型也可能存在，其特征是对哌唑嗪的亲和力较低。B)男性前列腺尿道中α _1-肾上腺素受体亚型mrna的定量和分布。我们通过RNase保护实验和原位杂交研究了人类男性后尿道中3种α _1-肾上腺素能受体亚型mrna （α _<1a, 1b, 1d>）的比例及其在尿道横断面上的定位。RNase保护实验显示，α _<1a>是男性前列腺尿道样本中主要的mRNA亚型。alpha_ < 1 d。在所有检测样本中均未检测到1b> mRNA。在男性前列腺尿道中，α _<1a>: α _<1b>: α _<1d>亚型mrna的丰度之比为100:0:0。2 .尿道平滑肌可见强烈的α _<1a>染色，而α _<1b>和α _<1d>染色较弱。在三个克隆的al亚型中，α _<1a>最有可能负责人类前列腺尿道的收缩。因此，α <12>的选择性药物治疗尿道疾病可能比非选择性药物更有效。少

A) Identification of alpha_1-adrenoceptor subtype in the human prostatic urethra1. To identify the alpha_1-adrenoceptor subtypes in the human prostatic urethra, we compared the potencies of various alpha_1-adrenoceptor agonists and antagonists in inhibiting [^3H] tamsulosin binding to human prostatic urethral membranes with their potencies in inhibiting the binding of [^<125>] HEAT to cloned human alpha_<1a>, alpha_<1b> and alpha_<1d>.2. The alpha_<1A>a-selective antagonists 5-methylurapidil and niguldipine showed higher affinities for both cloned alpha_<1a> and urethral alpha_1-adrenoceptorrs than for cloned alpha_<1b> and alpha_<1d>-adrenoceptors. alpha_<1A>- selective agonist also showed high affinity for the cloned alpha_<1a> subtype and urethral alpha_1-adrenoceptors. Prazosin showed lower affinity for alpha_1- adrenoceptors in the human prostatic urethra than for any of the three cloned alpha_1-adrenoceptors.3. Comparison of the affinities of alpha_1-adrenoceptor agonists and ant … More agonistws for human prostatic urethral alpha_1-adrenoceptors to their affinities for the three cloned alpha_1-subtypes indicated a close correlation between the affinities for human urethral alpha_1- and the cloned alpha_<1a>-adrenoceptors. However, prazosin did not conform to this pattern. These findings suggest that the predominant alpha_1-adrernoceptor in the human urethra is the alpha_<1A> subtype, and that an alpha_<1L> subtype which has been characterised by its low affinity for prazosin, may also be present.B) Quantification and distribution of alpha_1-adrenoceptor subtype mRNAs in mate prostatic urethra.1. We performed RNase protection assays and in situ hybridization to investigate the ratio of the three alpha_1-adrenoceptor subtype mRNAs, alpha_<1a, 1b, 1d> in the male human posterior urethra, and their localization in urethral cross-sections. As revealed by the RNase protection assays, alpha_<1a> was the predominant subtype mRNA in male prostatic urethral samples. alpha_<1d.1b> mRNA was was not detected in any of the samples tested. The ratio of the abundances of the subtype mRNAs, alpha_<1a> : alpha_<1b> : alpha_<1d>, was 100 : 0 : 0 in the male prostatic urethra.2. Intense alpha_<1a> staining observed in the smooth muscle of the urethra, but alpha_<1b> and alpha_<1d> staining was much less intense.3. Of the three cloned al subtypes, alpha_<1a> is the most likely to be responsible for the contraction of the human prostatic urethra. Therefore alpha_<12> selective drugs may be more efficacious than nonselective drugs for the treatment of urethral disorders. Less