Significance of transient receptor potential vanilloid 4 and aquaporin 5 co-expression in the rat uterus at term

AIMS: Aquaporins (AQPs) are channel proteins that facilitate the rapid passive movement of water. In our studies it was proved that the decreased AQP5 expression is followed by the increase of uterine contractility. The transient receptor potential vanilloid 4 (TRPV4) is a calcium channel, which is activated in response to osmotic changes. Our aim was to determine the possible role of AQP5 in this osmotic regulation of TRPV4, thus in pregnant uterine contraction. MAIN METHODS: We used RT-PCR and Western blot techniques for the detection of the TRPV4 expression during pregnancy in rat uterus. The localization of AQP5 and TRPV4 was determined by immunohistochemical studies. The role of TRPV4 in uterus contraction was investigated in an isolated organ bath system. In vitro uterus contractions were stimulated with KCl and its effect was investigated with the selective TRPV4 agonist (RN1747) and antagonist (RN1734). KEY FINDINGS: The TRPV4 expression continuously increased from day 18 to the last day of pregnancy. The co-expression of TRPV4 and AQP5 in the myometrium and endometrium was determined in the late pregnant uterus. The TRPV4 antagonist and agonist significantly decreased and increased uterine contraction, respectively, especially on the last day of pregnancy. SIGNIFICANCE: We presume the decreased AQP5 expression triggers hypertonic stress, which activates TRPV4 and increases uterus contraction on the day of labor. Based on these findings, we suppose the TRPV4 effect on uterus contraction is AQP5 control, which could be a new target in preterm birth therapy.