title: Hormonal modulation of benzodiazepines' actions on rat isolated uterus.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: M K
authors.initials: MK
authors.lastname: Yiu
authors.forename: Y W
authors.initials: YW
authors.lastname: Kwan
authors.forename: M P
authors.initials: MP
authors.lastname: Ngan
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000819:agonists / Q000494:pharmacology*; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000819:agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology; D014599:Uterus / Q000187:drug effects* / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D004338:Drug Combinations; D004967:Estrogens; D007546:Isoquinolines; D011963:Receptors, GABA-A; D011374:Progesterone; D002998:Clonazepam; D003975:Diazepam; C037850:PK 11195