Comparison of cloned and pharmacologically defined rat tissue alpha 1-adrenoceptor subtypes.
Comparison of cloned and pharmacologically defined rat tissue alpha 1-adrenoceptor subtypes.
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克隆和药理学定义的大鼠组织 α1-肾上腺素受体亚型的比较。
DOI：
10.1007/bf00241087
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Insel,PA
中科院分区：
文献类型：
--
作者：
Michel,MC;Insel,PA
多种α1肾上腺素受体亚型已被药理学和受体克隆技术确定，但克隆和药理学定义的亚型的精确对齐仍不清楚。我们比较了8种亚型选择性化合物对3种克隆的α1肾上腺素受体亚型（大鼠α 1 B、牛α 1 Crat α 1 A/D）的亲和力，并与先前在大鼠脾脏、大脑皮质和肾脏中用相同方法测定的亲和力进行了比较（Naunyn-Schmiedeberg's Arch. Pharmacol. 348：385-395，1993）。在迄今为止对克隆的α1-肾上腺素受体亚型进行测试的所有化合物中，（+）-坦索罗辛似乎是最具选择性的，效力等级为α1C> α1A/D≥ α1B。α 1A-选择性5-甲基-乌拉地尔、甲氧胺、羟甲唑啉、酚妥拉明和（-）-和（+）-坦索罗辛以及去甲肾上腺素和SDZ NVI-085在脾脏α 1B-肾上腺素受体及其在大脑皮质和肾脏中的低亲和力位点的亲和力与克隆的α 1B-肾上腺素受体的亲和力最相关。这些药物在大脑皮层高亲和力位点（药理学定义的α 1A-肾上腺素受体）的亲和力与克隆的α 1C-肾上腺素受体的亲和力最匹配。大鼠肾脏似乎含有两种氯乙基可乐定抗性α1肾上腺素受体亚型，其中一种与克隆的α1C-相似，另一种与克隆的α1A/D-肾上腺素受体相似。我们的结论是，克隆的α 1B-肾上腺素受体是药理学定义的α 1B-肾上腺素受体的遗传相关。在大鼠肾脏中存在与克隆的α 1 A/D受体相对应的α1受体亚型。在克隆的α1-肾上腺素受体亚型中，牛α 1C-肾上腺素受体与大鼠皮质中药理学定义的α 1A-肾上腺素受体和大鼠肾脏中氯乙基可乐定不敏感亚型之一最相似。
Multiple α1-adrenoceptor subtypes have been defined by pharmacological and receptor cloning techniques, but the precise alignment of cloned and pharmacologically-defined subtypes is still unclear. We have compared the affinities of 8 subtype-selective compounds at three cloned α1-adrenoceptor subtypes (rat α1B, bovine α1Crat α1A/D) with those previously determined by the same methods in rat spleen, cerebral cortex, and kidney (Naunyn-Schmiedeberg's Arch. Pharmacol. 348: 385–395, 1993). Among all compounds tested to date at cloned α1-adrenoceptor subtypes (+)-tamsulosin appears to be the most selective with a rank order of potency α1C> α1A/D≥ α1B. Affinities for the α1A-selective 5-methyl-urapidil, methoxamine, oxymetazoline, phentolamine and (−)- and (+)-tamsulosin and for noradrenaline and SDZ NVI-085 at the splenic α1B-adrenoceptors and at their low affinity sites in cerebral cortex and kidney correlated best with those at the cloned α1B-adrenoceptor. Affinities of these drugs at their high affinity sites in cerebral cortex (pharmacologically-defined α1A-adrenoceptor) were matched best by those at the cloned α1C-adrenoceptor. Rat kidney appears to contain two chloroethylclonidine-resistant α1-adrenoceptor subtypes one of which is similar to the cloned at α1C- and one to the cloned α1A/D-adrenoceptor. We conclude that the cloned α1B-adrenoceptor is the genetic correlate of the pharmacologically-defined α1B-adrenoceptor. An α1-adrenoceptor subtype corresponding to the cloned α1A/D-adrenoceptor appears to exist in rat kidney. Among cloned α1-adrenoceptor subtypes, the bovine α1C-adrenoceptor bears the closest resemblance to the pharmacologically-defined α1A-adrenoceptor in rat cortex and to one of the chloroethylclonidine-insensitive subtypes in rat kidney.