Büscher R, Insel P A, Michel M C
Dept. Medicine, University of Essen, Germany.
Life Sci. 1994;54(14):999-1007. doi: 10.1016/0024-3205(94)00502-8.
SDZ NVI-085 has been proposed to be a centrally acting agonist with selectivity for some alpha 1-adrenoceptor subtypes. We have investigated its selectivity and efficacy at alpha 1-adrenoceptor subtypes in rat tissues and at cloned subtypes. SDZ NVI-085 had higher affinity for chloro-ethylclonidine-insensitive (alpha 1A-like) than for -sensitive (alpha 1B) alpha 1-adrenoceptors in rat kidney but not in cerebral cortex. SDZ NVI-085 recognized cloned alpha 1-adrenoceptor subtypes expressed in COS cells with the order of potency bovine alpha 1C > rat alpha 1A/D > rat alpha 1B. Relative to 100 microM noradrenaline, SDZ NVI-085 was only a partial agonist for stimulation of inositol phosphate formation in rat kidney and inhibited noradrenaline-stimulated inositol phosphate formation in native and chloroethylclonidine-treated tissue. We conclude that SDZ NVI-085 discriminates among multiple alpha 1-adrenoceptor subtypes and is a partial agonist at rat renal alpha 1A- and alpha 1B-adrenoceptors.
SDZ NVI - 085被认为是一种对某些α1 - 肾上腺素能受体亚型具有选择性的中枢作用激动剂。我们已经研究了它在大鼠组织中的α1 - 肾上腺素能受体亚型以及克隆亚型上的选择性和效能。在大鼠肾脏中，SDZ NVI - 085对氯乙基可乐定不敏感（α1A样）的α1 - 肾上腺素能受体的亲和力高于对敏感（α1B）的α1 - 肾上腺素能受体，但在大脑皮层中并非如此。SDZ NVI - 085识别在COS细胞中表达的克隆α1 - 肾上腺素能受体亚型，其效力顺序为牛α1C > 大鼠α1A/D > 大鼠α1B。相对于100微摩尔去甲肾上腺素，SDZ NVI - 085在刺激大鼠肾脏中肌醇磷酸形成方面只是一种部分激动剂，并且在天然组织和氯乙基可乐定处理的组织中抑制去甲肾上腺素刺激的肌醇磷酸形成。我们得出结论，SDZ NVI - 085能区分多种α1 - 肾上腺素能受体亚型，并且是大鼠肾脏α1A - 和α1B - 肾上腺素能受体的部分激动剂。
