Proestrus and metestrus rat uterus, a rapid and simple in vitro method for detecting histamine H2-receptor antagonism.

The antagonism caused by metiamide and cimetidine on histamine-induced inhibition of spontaneous and electrically stimulated isometric contractions of superfused rat uterine horns from proestrus and metestrus stages was studied in vitro. Histamine depressed smooth muscle "twitch" responses of spontaneously contracting or electrically stimulated uterine preparations of both stages in the same dose-dependent manner. The typical effects of organ relaxation, inhibition of contraction height and reduction of resting tension generated by histamine, could both be antagonized by the histamine H2-receptor blockers metiamide and cimetidine, while both compounds failed to reverse orciprenaline- or isoproterenol-induced inhibition of uterine contractility. Diphenhydramine, a histamine H1-receptor antagonist, was not able to reduce histamine-induced inhibition of uterine contractions, thereby confirming that the histamine receptors of the rat uterine tissue are H2 in type. Furthermore, beta-adrenergic blockers, like propranolol and dichloroisoproterenol, failed to antagonize the decrease in contraction amplitude but prevented fall in resting tension induced by histamine. Tyramine, cAMP or dibutyryl-cAMP produced no inhibition of motility of the isolated uterine tissue. Possible mechanisms of these findings are discussed. The findings show that the isolated non-estrus rat uterus is useful as a rapid method for investigating specific effects of drugs designated for potential histamine H2-receptor antagonism. This preparation offers the additional advantage that no interference with beta-blockers occurs.