3H-哌唑嗪和3H-育亨宾与豚鼠胃中α肾上腺素能受体的结合

The bindings of 3H-prazosin and 3H-yohimbine to alpha adrenoceptors in the guinea-pig stomach.

作者信息

Taniguchi T, Nishikawa H, Yokotani K, Fujiwara M

机构信息

Department of Pharmacology, Faculty of Midicine, Kyoto University, Japan.

出版信息

Life Sci. 1988;42(23):2341-7. doi: 10.1016/0024-3205(88)90187-7.

DOI:10.1016/0024-3205(88)90187-7

PMID:2836683

Abstract

Alpha adrenoceptor subtypes have been investigated by radioligand binding study in guinea-pig stomach using 3H-prazosin and 3H-yohimbine. The specific 3H-prazosin binding to guinea-pig stomach was saturable and of high affinity (KD = 1.4 nM) with a Bmax of 33 fmol/mg protein. Specific 3H-yohimbine binding to the tissue was also saturable and of high affinity (KD = 25.5 nM) with a Bmax of 150 fmol/mg protein. Adrenergic drugs competed for 3H-prazosin binding in order of prazosin greater than phentolamine greater than methoxamine greater than norepinephrine greater than clonidine greater than epinephrine greater than yohimbine. These drugs competed for 3H-yohimbine binding in order of yohimbine greater than phentolamine greater than clonidine greater than epinephrine greater than norepinephrine greater than prazosin greater than greater than prazosin greater than methoxamine. We also examined whether dopamine receptors exist in guinea-pig stomach, using radioligand binding study. Specific binding of 3H-spiperone, 3H-apomorphine, 3H-dopamine and 3H-domperidone was not detectable in the stomach. Dopaminergic drugs such as dopamine, haloperidol, domperidone and sulpiride competed for 3H-prazosin binding in order of haloperidol greater than domperidone greater than dopamine greater than sulpiride. Metoclopramide, sulpiride and dopamine competed for 3H-yohimbine binding in order of metoclopramide greater than sulpiride greater than dopamine. These results suggest that guinea-pig stomach has alpha 1 and alpha 2 adrenoceptors and has no specific dopamine receptors. It is also suggested that some dopamine receptor antagonists such as domperidone, haloperidol, sulpiride and metoclopramide have antagonistic actions on alpha adrenoceptors.

摘要

已使用³H-哌唑嗪和³H-育亨宾，通过放射性配体结合研究在豚鼠胃中研究了α肾上腺素能受体亚型。³H-哌唑嗪与豚鼠胃的特异性结合具有饱和性且亲和力高（KD = 1.4 nM），Bmax为33 fmol/mg蛋白质。³H-育亨宾与该组织的特异性结合也具有饱和性且亲和力高（KD = 25.5 nM），Bmax为150 fmol/mg蛋白质。肾上腺素能药物对³H-哌唑嗪结合的竞争顺序为：哌唑嗪＞酚妥拉明＞甲氧明＞去甲肾上腺素＞可乐定＞肾上腺素＞育亨宾。这些药物对³H-育亨宾结合的竞争顺序为：育亨宾＞酚妥拉明＞可乐定＞肾上腺素＞去甲肾上腺素＞哌唑嗪＞甲氧明。我们还使用放射性配体结合研究检查了豚鼠胃中是否存在多巴胺受体。在胃中未检测到³H-螺哌隆、³H-阿扑吗啡、³H-多巴胺和³H-多潘立酮的特异性结合。多巴胺、氟哌啶醇、多潘立酮和舒必利等多巴胺能药物对³H-哌唑嗪结合的竞争顺序为：氟哌啶醇＞多潘立酮＞多巴胺＞舒必利。甲氧氯普胺、舒必利和多巴胺对³H-育亨宾结合的竞争顺序为：甲氧氯普胺＞舒必利＞多巴胺。这些结果表明，豚鼠胃具有α1和α2肾上腺素能受体，且没有特异性多巴胺受体。还表明，一些多巴胺受体拮抗剂，如多潘立酮、氟哌啶醇、舒必利和甲氧氯普胺，对α肾上腺素能受体具有拮抗作用。