The inhibitory effect of clonidine on the oestrogen-primed rat isolated uterus

The investigation was undertaken to study the mechanism of the inhibitory effects of clonidine on the oestrogen-primed rat isolated uterus. Clonidine produced dose-dependent relaxations of the rat isolated uterus which were competitively blocked by yohimbine but not by prazosin. Metiamide, a specific H2-histamine receptor antagonist, inhibited clonidine-induced responses only at a high concentration (1.0 X 10(-6)M). Propranolol, a beta-adrenoreceptor antagonist produced competitive antagonism of the clonidine responses. Like clonidine, noradrenaline also produced dose dependent relaxations of the rat isolated uterus. The responses to noradrenaline were not antagonized by either prazosin or yohimbine but were competitively antagonized by propranolol. The responses to clonidine were significantly inhibited by reserpine pretreatment (5 mg/kg; i.p., 24 h before) whilst responses to noradrenaline were significantly increased by this treatment. It is concluded that clonidine inhibits the uterus via an action on alpha 2-adrenoreceptors and possibly also to a lesser extent on H2-histamine receptors, leading ultimately to release of noradrenaline from endogenous stores which causes relaxation by acting on beta-adrenoreceptors.