Yiu M K, Kwan Y W, Ngan M P
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Eur J Pharmacol. 1996 Apr 29;302(1-3):99-108. doi: 10.1016/0014-2999(96)00070-2.
Effects of various benzodiazepines were investigated in ovariectomized rat isolated uterus which had been chronically pre-treated with different female sex hormones: oestrogen, progesterone and oestrogen + progesterone. Uteri obtained from all groups developed a spontaneous, rhythmic activity. The spontaneous activity observed in control uterus was either inhibited in a concentration-dependent manner by diazepam, 4'-chlorodiazepam, clonazepam or 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide (PK 11195), or was abolished in [Ca2+]o-free solution. Diazepam, 4'-chlorodiazepam, clonazepam and PK 11195 all caused a concentration-dependent relaxation of the [K+]o-pre-contracted uterus with the relative order of potency: PK 11195 > 4'-chlorodiazepam > diazepam > clonazepam. Administration of [Ca2+]o (1 microM to 10 mM) caused a concentration-dependent contraction of uterus, bathed in [Ca2+]o-free physiological salt solution obtained from different pre-treatment groups. Incubation with different concentrations (microM) of diazepam, 4'-chlorodiazepam, clonazepam and PK 11195 caused a decrease in response to [Ca2+]o-induced contraction in all groups of rat uteri. These results indicate that micromolar benzodiazepine binding sites exist in rat uterus. Diazepam, 4'-chlorodiazepam, clonazepam and PK 11195 caused relaxation of pre-contracted rat uterus and this effect may involve the inhibition of influx of [Ca2+]o and the relaxing effects of different benzodiazepines observed in this study can be modulated by pre-treatment with different female hormones.
在经不同雌性激素（雌激素、孕酮以及雌激素 + 孕酮）长期预处理的去卵巢大鼠离体子宫中，研究了各种苯二氮䓬类药物的作用。从所有组获得的子宫均表现出自发性节律活动。对照子宫中观察到的自发活动，要么被地西泮、4'-氯地西泮、氯硝西泮或1-(2-氯苯基)-N-甲基-N-(1-甲基丙基)-3-异喹啉甲酰胺（PK 11195）以浓度依赖性方式抑制，要么在无[Ca2+]o的溶液中消失。地西泮、4'-氯地西泮、氯硝西泮和PK 11195均导致[K+]o预收缩子宫出现浓度依赖性松弛，其效力相对顺序为：PK 11195 > 4'-氯地西泮 > 地西泮 > 氯硝西泮。给予[Ca2+]o（1微摩尔至10毫摩尔）会导致在来自不同预处理组的无[Ca2+]o生理盐溶液中浸泡的子宫出现浓度依赖性收缩。用不同浓度（微摩尔）的地西泮、4'-氯地西泮、氯硝西泮和PK 11195孵育，会导致所有组大鼠子宫对[Ca2+]o诱导收缩的反应降低。这些结果表明，大鼠子宫中存在微摩尔级苯二氮䓬结合位点。地西泮、4'-氯地西泮、氯硝西泮和PK 11195导致预收缩大鼠子宫松弛，这种作用可能涉及抑制[Ca2+]o内流，并且本研究中观察到的不同苯二氮䓬类药物的松弛作用可通过不同雌性激素的预处理来调节。
