Effects of trpv4 channel in pregnant and non-pregnant rat uterine tissue induced by oxytocin receptor desensization

Oxytocin is the most important hormone in the labor. It is responsible for the regulation of uterine contractions. Continuous exposure to high doses oxytocin causes oxytocin receptor desensitization. Oxytocin desensitization causes postpartum haemorrhage (PPH), which is caused by failure in the contraction of the uterus following delivery (uterine atony). These limitations in the use of oxytocin have led to need for new therapeutic targets in the regulation of uterine contractions. Transient receptor potantial (TRP) channels' are superfamily of cation channels mostly permeable to calcium. In recent years studies have shown that the presence of transient receptor potantial vanilloid 4 (TRPV4) channels, a member of this family, are present in uterine myometrial tissues. It was also found that mRNA and protein levels of these channels are increased with pregnancy. Studies have shown that TRPV4 channel antagonists can be used to reduce uterine contractions and prevent preterm labor. TRPV4 channel agonist GSK1016790A have also been shown to increase contractions rat uterus. However, no study has been done on the role of these channels in oxytocin desensitization. In this study, uterus strips obtained from pregnant and nonpregnant rats, who developed Oxytocin desensitization in isolated organ bath environment, were exposed to TRPV4 agonist and antagonist. Uterus contractions were recorded and the effects of these channels in Oxytocin desensitization on uterine tissue were investigated. In pregnant and non pregnant rats, it was determined that GSK1016790A increased contractions as much as oxytocin in oxytocin desensitized tissues, and cumulative oxytocin administration in the presence of GSK1016790A in organ bath was more effective that oxytocin administration alone. It is thought that this effect is due to the fact that they increase the intracelular Ca+² level by different mechanisms.