Mechanism of action of histamine in the estrogen-primed rat uterus

Abstract

Histamine produced a dose-dependent relaxation of uterine strips obtained from the estrogen-primed rat uterus. The responses to histamine were blocked competitively by metiamide (10 −8 −10 −8M), a specific H 2-receptor antagonist. Propranolol, a selective β-receptor blocker also produced competitive antagonism of the responses to histamine in the same dose range (10 −8−10 −6 M). The pA 2 value obtained for metiamide (8.9) was not significantly different from that obtained for propranolol (8.6). Nialamide (2.2 × 10 −6 M), the monoamine oxidase inhibitor, and cocaine (4.3 × 10 −6 M), the selective noradrenaline uptake blocker, potentiated the responses to histamine. However bretylium (2.4 × 10 −5 M), an adrenergic neuron blocker inhibited the responses to histamine. The combined effect of tyramine and histamine was found to be additive. Our data suggest that the histamine-induced relaxation of rat uterus may be produced through the stimulation of presynaptic H 2-receptors which causes the release of noradrenaline. The released noradrenaline acts on the postsynaptic β-receptors and produces relaxation of the rat uterus.