The effects of SB 216469, an antagonist which discriminates between the α1A‐adrenoceptor and the human prostatic α1‐adrenoceptor
The effects of SB 216469, an antagonist which discriminates between the α1A‐adrenoceptor and the human prostatic α1‐adrenoceptor
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SB 216469（一种区分 α1A 肾上腺素受体和人前列腺 α1 肾上腺素受体的拮抗剂）的作用
DOI：
10.1111/j.1476-5381.1996.tb16009.x
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发表时间：
1996
影响因子：
7.3
通讯作者：
Martin C. Michel
中科院分区：
文献类型：
--
作者：
R. Chess;Christopher R. Chapple;F. Verfurth;A. J. Noble;C. Couldwell;Martin C. Michel
1α1受体拮抗剂SB 216469(又称REC15/2739)在天然和克隆的α1受体亚型和在分离组织中的功能性α1受体亚型上的亲和力已被确定。2放射性配基结合研究表明，Sb 216469与大鼠大脑皮层和肾脏的α1A受体有较高的亲和力(9.5~9.8)，而在大鼠脾和肝脏的α1B受体上亲和力较低(7.7~8.2)。3在COS-1细胞中瞬时表达的克隆大鼠α1肾上腺素能受体亚型和稳定转染大鼠细胞中的克隆人α1肾上腺素能受体亚型中，SB 216469在α1a受体上亲和力高(9.6~10.4)，在α1b受体上亲和力低(8.0~8.4)，在α1d受体上亲和力中等(8.7~9.2)。4在功能性α1受体上，SB 216469具有相似的药理作用，在大鼠输精管和尾尾肌的α1A受体上亲和力较高(PA2=9.5~10.0)，在大鼠脾(6.7)和豚鼠主动脉的aα1B受体上亲和力低(6.7)和在大鼠主动脉的α1D受体上亲和力中等(8.8)。5最近的几项研究得出结论，存在于人前列腺中的α1-肾上腺素能受体具有α-α1A-肾上腺素能受体亚型的药理学特征。然而，在分离的组织条上测定的SB 216469与人前列腺α1-肾上腺素能受体的亲和力(PA2=8.1)，显著低于在放射性配基结合和大鼠功能研究中克隆的a-α1a-肾上腺素能受体(人、大鼠、牛)或天然α1A-肾上腺素能受体的亲和力。6因此，我们对SB 216469的结果表明，介导人前列腺收缩反应的α1-肾上腺素能受体具有区别于克隆的αα-肾上腺素能受体或天然的α1-肾上腺素能受体的特性。由于先前已证明该受体不是α1B或α1D肾上腺素受体，人前列腺的功能性αα1肾上腺素受体可能代表一种新的受体，其特性不同于目前用药物手段定义的任何α1肾上腺素受体。
1 The affinity of the α1‐adrenoceptor antagonist SB 216469 (also known as REC 15/2739) has been determined at native and cloned α1‐adrenoceptor subtypes by radioligand binding and at functional α1adrenoceptor subtypes in isolated tissues. 2 In radioligand binding studies with [3H]‐prazosin, SB 216469 had a high affinity at the α1A‐adrenoceptors of the rat cerebral cortex and kidney (9.5–9.8) but a lower affinity at the α1B‐adrenoceptors of the rat spleen and liver (7.7–8.2). 3 At cloned rat α1‐adrenoceptor subtypes transiently expressed in COS‐1 cells and also at cloned human a α1‐adrenoceptor subtypes stably transfected in Rat‐1 cells, SB 216469 exhibited a high affinity at the α1a‐adrenoceptors (9.6–10.4) with a significantly lower affinity at the αlb‐adrenoceptor (8.0–8.4) and an intermediate affinity at the α1d‐adrenoceptor (8.7–9.2). 4 At functional α1‐adrenoceptors, SB 216469 had a similar pharmacological profile, with a high affinity at the α1A‐adrenoceptors of the rat vas deferens and anococcygeus muscle (pA2 = 9.5–10.0), a low affinity at the a α1B‐adrenoceptors of the rat spleen (6.7) and guinea‐pig aorta (8.0), and an intermediate affinity at the α1D‐adrenoceptors of the rat aorta (8.8). 5 Several recent studies have concluded that the α1‐adrenoceptor present in the human prostate has the pharmacological characteristics of the a α1A‐adrenoceptor subtype. However, the affinity of SB 216469 at human prostatic α1‐adrenoceptors (pA2 = 8.1) determined in isolated tissue strips, was significantly lower than the values obtained at either the cloned a α1a‐adrenoceptors (human, rat, bovine) or the native α1A‐adrenoceptors in radioligand binding and functional studies in the rat. 6 Our results with SB 216469, therefore, suggest that the α1‐adrenoceptor mediating contractile responses of the human prostate has properties which distinguish it from the cloned αla‐adrenoceptor or native a α1‐adrenoceptor. Since it has previously been shown that the receptor is not the α1B‐ or α1D‐adrenoceptor, the functional a α1‐adrenoceptor of the human prostate may represent a novel receptor with properties which differ from any of the α1‐adrenoceptors currently defined by pharmacological means.
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影响因子：
3.6
作者：
C. Forray;J. Bard;J. Wetzel;G. Chiu;E. Shapiro;R. Tang;H. Lepor;P. Hartig;R. Weinshank;T. Branchek
通讯作者：
C. Forray;J. Bard;J. Wetzel;G. Chiu;E. Shapiro;R. Tang;H. Lepor;P. Hartig;R. Weinshank;T. Branchek
牛α1C-肾上腺素受体的大鼠同源物的克隆、表达和组织分布为其分类为α1A亚型提供了证据。
影响因子：
3.6
作者：
Perez,DM;Piascik,MT;Malik,N;Gaivin,R;Graham,RM
通讯作者：
Graham,RM
α1A-肾上腺素受体 cDNA 的分子克隆和表达。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lomasney,JW;Cotecchia,S;Lorenz,W;Leung,WY;Schwinn,DA;Yang-Feng,TL;Brownstein,M;Lefkowitz,RJ;Caron,MG
通讯作者：
Caron,MG
新型 α1-肾上腺素能受体亚型 cDNA 的分子克隆和表达。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Schwinn,DA;Lomasney,JW;Lorenz,W;Szklut,PJ;FremeauJr,RT;Yang-Feng,TL;Caron,MG;Lefkowitz,RJ;Cotecchia,S
通讯作者：
Cotecchia,S