Hiraoka Y, Ohmura T, Oshita M, Watanabe Y, Morikawa K, Nagata O, Kato H, Taniguchi T, Muramatsu I
Research and Development Division, Hokuriku Seiyaku, Katsuyama, Fukui, Japan.
Eur J Pharmacol. 1999 Jan 29;366(1):119-26. doi: 10.1016/s0014-2999(98)00895-4.
The alpha1-adrenoceptor subtypes of rat prostate were characterized in binding and functional experiments. In binding experiments, [3H]tamsulosin bound to a single class of binding sites with an affinity (pKD) of 10.79+/-0.04 and Bmax of 87+/-2 fmol mg(-1) protein. This binding was inhibited by prazosin, 2-(2,6-dimethoxy-phenoxyethyl)-aminomethyl-1,4-benzodioxane hydrochloride (WB4101), 5-methylurapidil, alpha-ethyl-3,4,5,-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)-amin o)-propyl)benzeneacetonitrile fumarate (HV723) and oxymetazoline with high efficacy, resulting in a good correlation with the binding characteristics of cloned alpha1a but not alpha1b and alpha1d-adrenoceptor subtypes. In functional studies, noradrenaline and oxymetazoline produced concentration-dependent contractions. These contractions were antagonized by tamsulosin, prazosin, WB4101 and 5-methylurapidil with an efficacy lower than that exhibited by these agents for inhibition of [3H]tamsulosin binding. The relationship between receptor occupancy and contractile amplitude revealed the presence of receptor reserve for noradrenaline, but the contraction induced by oxymetazoline was not in parallel with receptor occupation and developed after predicted receptor saturation. From these results, it is suggested that alpha1A-adrenoceptors are the dominant subtype in the rat prostate which can be detected with [3H]tamsulosin, but that the functional subtype mediating adrenergic contractions has the characteristics of the alpha1L-adrenoceptor subtype, having a lower affinity for prazosin and some other drugs than the alpha1A-adrenoceptor subtype.
通过结合实验和功能实验对大鼠前列腺中的α1-肾上腺素能受体亚型进行了表征。在结合实验中，[3H]坦索罗辛与一类结合位点结合，亲和力（pKD）为10.79±0.04，最大结合容量（Bmax）为87±2 fmol mg(-1)蛋白质。哌唑嗪、2-(2,6-二甲氧基苯氧基乙基)-氨基甲基-1,4-苯并二恶烷盐酸盐（WB4101）、5-甲基尿嘧啶、富马酸α-乙基-3,4,5-三甲氧基-α-(3-((2-(2-甲氧基苯氧基)乙基)-氨基)-丙基)苯乙腈（HV723）和羟甲唑啉能高效抑制这种结合，这与克隆的α1a而非α1b和α1d-肾上腺素能受体亚型的结合特性具有良好的相关性。在功能研究中，去甲肾上腺素和羟甲唑啉产生浓度依赖性收缩。这些收缩被坦索罗辛、哌唑嗪、WB4101和5-甲基尿嘧啶拮抗，但其拮抗效力低于这些药物对[3H]坦索罗辛结合的抑制效力。受体占有率与收缩幅度之间的关系表明，去甲肾上腺素存在受体储备，但羟甲唑啉诱导的收缩与受体占有率不平行，且在预测的受体饱和后才出现。从这些结果表明，α1A-肾上腺素能受体是大鼠前列腺中的主要亚型，可用[3H]坦索罗辛检测到，但介导肾上腺素能收缩的功能亚型具有α1L-肾上腺素能受体亚型的特征，对哌唑嗪和其他一些药物的亲和力低于α1A-肾上腺素能受体亚型。
