The effects of histamine on the isolated mouse uterus

Abstract

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.

First-trimester antihistamine exposure and risk of spontaneous abortion or preterm birth

“…Pennefather and colleagues reported similar findings by comparing medication effects in uterine segments from pregnant and nonpregnant women; they saw a pregnancy‐related increase in the myometrial response when stimulated by histamine. Several animal studies have confirmed these findings . Antihistamines may interfere with these uterine contractile or early‐pregnancy processes and contribute to adverse pregnancy outcomes, such as SAB and PTB.…”

“…Several animal studies have confirmed these findings. 13,14 Antihistamines may interfere with these uterine contractile or earlypregnancy processes and contribute to adverse pregnancy outcomes, such as SAB and PTB.…”

“…Histamine receptors are found on the trophoblast and help mediate the implantation of the blastocyst . Receptors are also found on uterine smooth muscle cells where they play a role in contraction (H1) and relaxation (H2) . Both implantation and contractile pathways are inhibited when antihistamines were tested in animal studies .…”

“…4,7 Receptors are also found on uterine smooth muscle cells where they play a role in contraction (H1) and relaxation (H2). 5,8,13,14 Both implantation and contractile pathways are inhibited when antihistamines were tested in animal studies. 8 Because of the role of histamine and its receptors in these processes, it is reasonable to conclude that antihistamine use may be associated with pregnancy outcomes such as spontaneous abortion (SAB) and preterm birth (PTB).…”

Chlamydia muridarum infection differentially alters smooth muscle function in mouse uterine horn and cervix

“…Histamine is one of the mediators released during mast-cell degranulation and it is also a potent modulator of smooth muscle contraction along the female reproductive tract (16,59). Thus, the effects of Cmu infection on the cervical and uterine contractions to histamine were also investigated.…”