Relations between the effects of histamine,pheniramin and metiamide on spontaneous motility and the formation of cyclic AMP in the isolated rat uterus

Summary Histamine (5×10^–6 to 10^–3M) depressed the spontaneous motility of the isolated rat uterus in a dose-dependent manner. Under these conditions uterine cyclic AMP was raised up to 92%. Both effects, uterine relaxation and cyclic AMP accumulation after 2 min could be inhibited dose dependently by the H₂-antihistaminic compound metiamide (1.7×10^–6 M to 1.7×10^–4 M). By contrast, the H₁-antagonist pheniramin (4.4×10^–5 M) was ineffective. It was concluded that the histamine-induced inhibition of rat uterine motility is mediated by cyclic AMP which is formed in response to stimulation of H₂-histaminergic receptors.