Characterization of prostatic alpha-l adrenoceptors in human benign prostatic hypertrophy.

为了鉴定和表征人前列腺中的α-1肾上腺素受体，测定了良性前列腺肥大（BPH）患者粗前列腺膜中[^3 H]哌唑嗪和[^3 H]布纳唑嗪的特异性结合。[^3H]哌唑嗪和[^3H]布那唑嗪的特异性结合是可饱和的、可逆的和高亲和力的（Kd值分别为0.35 nM和1.03 nM），并且它显示出药理学特异性以及立体选择性，这是α-1肾上腺素受体的特征。α-1拮抗剂与两种放射性配体竞争人前列腺中的结合位点，顺序为：YM 617>哌唑嗪>布那唑嗪>特拉唑嗪>萘哌地尔>乌拉地尔。α-1拮抗剂在人前列腺中竞争放射性配体结合位点的效力（pKi）与其在前列腺中的药理效力（pA_2）具有良好的相关性。Scatchard分析表明，哌唑嗪、布那唑嗪和萘哌地尔对前列腺[^3H]哌唑嗪结合的降低是由于三种药物对前列腺[^3H]哌唑嗪结合的显著增加， ...更多信息 在Kd值中没有Bmax值的变化。此外，哌唑嗪对[^3H]哌唑嗪特异性结合的抑制作用在人前列腺和主动脉中是相同的，但YM 617在人前列腺中的抑制作用比在主动脉中强约14倍。氯乙可乐定处理抑制了两种组织中[^3H]哌唑嗪的部分特异性结合，从而表明α 1肾上腺素受体亚型共存（α-1a和α-1b）：与无BPH的正常组织相比，BPH肥大前列腺中[^3 H]哌唑嗪和[^3 H]布那唑嗪的最大结合位点数显著增加，而BPH对两种放射性配体的解离常数几乎没有影响。此外，在人前列腺中α 1肾上腺素受体结合位点的区域变化顺序为：内区>外区>前列腺尿道。1）[^3H]哌唑嗪和[^3H]布那唑嗪选择性标记人前列腺中的α-1肾上腺素受体，2）α-1拮抗剂如YM 617和哌唑嗪拮抗α-1肾上腺素受体（以竞争性和可逆的方式）具有高亲和力，3）YM 617是人前列腺中α-1肾上腺素受体的相对选择性拮抗剂，而不是人主动脉中的α-1肾上腺素受体，以及4）在人前列腺中存在更大的α-1肾上腺素受体密度。1肾上腺素受体位点。少

To identify and charaterize alpha-1 adrenoceptors in human prostates, specific binding of [^3H] prazosin and [^3H] bunazosin in crude prostatic membranes from patients with benign prostatic hypertrophy (BPH) was measured. Specific binding of [^3H] prazosin and [^3H] bunazosin was saturable, reversible and of high affinity (Kd values=0.35 nM and 1.03 nM, respectively), and it showed a pharmacological specificity as well as stereoselectivity which characterized alpha-1 adrenoceptors. Alpha-1 antagonists competed with both radioligands for the binding sites in human prostates in order : YM617 > prazosin > bunazosin > terazosin > naftopidil > urapidil. The potencies (pKi) of alpha-1 antagonists in competing for the radioligand binding sites in human prostates correlated well with their pharmacological potencies (pA_2) in the prostates. Scatchard analysis indicated that the decrease of prostatic [^3H] prazosin binding by prazosin, bunazosin and naftopidil was due to a significant in-crease … More in the Kd value without a change in the Bmax value. Also, the inhibitory effect of specific [^3H] prazosin binding by prazosin was identical in human prostate and aorta, but that by YM617 was approximately 14 times more potent in human prostate than in the aorta. Chlorethylclonidine treatment inhibited partially specific [^3H] prazosin binding in both tissues, thereby suggesting the coexistence of alpha-1 adrenoceptor subtypes (alpha-la and alpha-1b).There was a significant increase in the maximal number of binding sites for [^3H] prazosin and [^3H] bunazosin in hypertrophied prostates from BPH compared to normal tissues without BPH, whereas BPH had little effect on the dissociation constants for both radioligands. Also, there was a regional variation of alpha-1 adrenoceptor binding sites in the human prostate in order : inner zone > outer zone > prostatic urethra.Thus, we conclude : 1) [^3H] prazosin and [^3H] bunazosin selectively labels alpha-1 adrenoceptors in human prostates, 2) alpha-1 antagonists such as YM617 and prazosin antagonizes alpha-1 adrenoceptors (in a competitive and reversible manner) with high affinity, 3) YM617 is relatively selective antagonist of alpha-1 adrenoceptors in human prostate than in human aorta and 4) there is a greater density of alpha-1 adrenoceptor sites in BPH. Less