Stimulation of contractions in pregnant human myometrium is associated with 5-HT3 receptors

Abstract

BackgroundSerotonin (5-HT) is known to play an important role in regulating uterine contractions. However, the specific receptors involved have not been well characterized. We evaluated whether 5-HT3 receptors exist in human myometrium, and their effects on myometrial contractility when stimulated by a 5-HT3 agonist. MethodsFour tissue samples taken from patients undergoing hysterectomy (n=2) and elective cesarean delivery (n=2) were used to detect expression of 5-HT3 receptors on the myometrium using western blotting. For isometric tension measurement, another 12 myometrial strips obtained from patients undergoing elective cesarean delivery were randomly divided into a control group (Group CON) and an RS56812 group (Group RG). In increasing doses from 10−7M to 10−4M, RS56812, a 5-HT3 receptor agonist, was used to investigate the contractile effects after bonding to the 5-HT3 receptor, following which the effects of granisetron were assessed. Amplitude, interval and duration of myometrial contractions were recorded. ResultsProteins with a molecular mass of 55kDa, consistent with 5-HT3 receptors, were detected both on non-pregnant and late-pregnant human uteri. RS56812 increased the contractile amplitude at concentrations of 10−6M, 10−5M and 10−4M, achieving maximum effect at 10−5M. A prolonged contractile interval was detected at the concentration of 10−4M. However, RS56812 showed no significant effect on contraction duration. Granisetron did not reverse the contractile effects induced by RS56812. Conclusion5-HT3 receptors are expressed on non-pregnant and pregnant uteri. RS56812 enhanced myometrial contractions, but this was not affected by granisetron, the mechanism of which requires further investigation.