HORMONAL MODULATION OF BENZODIAZEPINES ACTIONS ON RAT ISOLATED UTERUS

Effects of various benzodiazepines were investigated in ovariectomized rat isolated uterus which had been chronically pre-treated with diffe rent female sex hormones: oestrogen, progesterone and oestrogen + prog esterone. Uteri obtained from all groups developed a spontaneous, rhyt hmic activity. The spontaneous activity observed in control uterus was either inhibited in a concentration-dependent manner by diazepam, 4'- chlorodiazepam, clonazepam or ethyl-N-(1-methylpropyl)-3-isoquinolinec arboxamide (PK 11195), or was abolished in [Ca2+](0)-free solution. Di azepam, 4'-chlorodiazepam, clonazepam and PK 11195 all caused a concen tration-dependent relaxation of the [K+](0)-pre-contracted uterus with the relative ol der of potency: PK 11195 > 4'-chlorodiazepam diazepam > clonazepam. Administration of [Ca2+](0) (1 mu M to 10 mM) caused a concentration-dependent contraction of uterus, bathed in [Ca2+](0)-fre e physiological salt solution obtained from different pre-treatment gr oups. Incubation with different concentrations(mu M) of diazepam, 4'-c horodiazepam, clonazepam and PK 11195 caused a decrease in response to [Ca2+](0)-induced contraction in all groups of rat uteri. These resul ts indicate that micromolar benzodiazepine binding sites exist in rat uterus. Diazepam, 4'-chlorodiazepam, clonazepam and PK 11195 caused re laxation of pre-contracted rat uterus and this effect may involve the inhibition of influx of [Ca2+](0) and the relaxing effects of differen t benzodiazepines observed in this study can be modulated by pre-treat ment with different female hormones.