The effects of histamine on the isolated mouse uterus

1. A study is made of the contractile and relaxant effects, and mechanism of action, of histamine on isolated uterus from mice treated with diethylstilboestrol, employing acetylcholine and adrenaline as contractile and relaxant standard agents. 2. Concentration-response curves for histamine agonists were obtained in the absence and presence of selective histaminergic blocking drugs (clemizole, ranitidine and thioperamide) and indomethacin. A number of experiments were carried out in uterus from reserpinised mice. Concentration-response curves for acetylcholine and adrenaline were also obtained in the absence and presence of their selective antagonist (atropine and propranolol). 3. In isolated oestrogenised mouse uterus, histamine and acetylcholine produced a concentration-related contractile response. When the uterus was precontracted with KCl, histamine at lower doses produced a slight contraction, though in the presence of clemizole it induced concentration-related relaxation, reminiscent of that produced by adrenaline. Atropine and propranolol antagonised the contractile and relaxant effects of acetylcholine and adrenaline, respectively. 4. In isolated uterus from reserpinised mice, histamine and 2-pyridylethylamine, but not 4-methylhistamine, produced a concentration-related contractile response. Ranitidine potentiated the contractile effect of histamine, though clemizole--in the presence of ranitidine--competitively antagonised the contractile effect of histamine (pA2 = 10.50 +/- 0.81). The concentration-relaxant curve of histamine in the presence of clemizole was not modified by ranitidine or indomethacin, but shifted to the right with thioperamide. The same displacement was also observed in the presence of clemizole plus ranitidine. 5. In mouse isolated uterus, histamine mainly produced contraction mediated by histamine H1-receptors, though the existence of histamine H2- or H3-receptors mediating relaxation could not be excluded.