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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(-8) M), a specific H2-receptor antagonist. Propranolol, a selective beta-receptor blocker also produced competitive antagonism of the responses to histamine in the same dose range (10(-8)-10(-6) M). The pA2 value obtained for metiamide (8.9) was not significantly different from that obtained for propranolol (8.6). Nialamide (2.2 X 10(-6) M), the monoamine oxidase inhibitor, and cocaine (4.3 X 10(-6) M), the selective noradrenaline uptake blocker, potentiated the responses to histamine. However bretylium (2.4 X 10(-5) M), and 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 H2-receptors which causes the release of noradrenaline. The released noradrenaline acts on the postsynaptic beta-receptors and produces relaxation of the rat uterus.

The effects of histamine and its analogs 2-(2-pyridyl) ethylamine (PEA) and 4-methylhistamine (4 MH) have been studied on uterine preparations obtained from estrogen-primed guinea pigs and rats. (1) Histamine and 4 MH, a specific H2-receptor agonist produced relaxation in estrogen-primed rat uterus, whereas these agonists produced contraction in the estrogen-primed guinea pig uterus. (2) PEA, a specific H1-receptor agonist produced contraction in the guinea pig uterus but had no effect on the rat uterus. (3) Metiamide blocked responses to histamine and 4 MH in the rat uterus, whereas mepyramine blocked responses to histamine and PEA in the guinea pig uterus. (4) Propranolol produced competitive antagonism with histamine in the rat uterus, whereas it had no significant effect on the histamine or PEA responses in the guinea pig uterus. (5) Reserpine pretreatment completely abolished the responses to histamine and 4 MH in the rat uterus but did not alter the response in the guinea pig uterus. (6) Our data suggest that in rat uterus only H2-receptors are present and they are indirectly through the release of noradrenaline. In the guinea pig uterus both H1- and H2-receptors are present and are excitatory and directly acting.

Histamine, 4-methylhistamine, 3-(beta-aminoethyl)-1,2,4 triazole and betazole, in that order, stimulated adenylate cyclase prepared from rat gastric tissue in a dose-dependent manner. Burimamide, an H(2)-receptor blocking agent, in concentrations of 1-5 x 10(-6) M antagonized this effect. The data lend some support to the hypothesis that elevated levels of cyclic adenosine 3',5'-monophosphate may be involved in histamine-stimulated gastric secretions and that H(2)-receptors are associated with adenylate cyclase.

Histamine and three histamine analogs (4-methylhistamine, 3-beta-aminoethyl 1,2,4 triazole (TD) and betazole) all produced relaxation in depolarized rat uterine strips. The rank order obtained was the same as that noted previously in the heart and gastric mucosa and the effects of the agonists were blocked by burimamide. The uterine histamine receptor thus appears to be of the H2-type. Adenylate cyclase prepared from the uterus was not stimulated by histamine. Uterine H2-receptors thus do not appear to be associated with adenylate cyclase.