The Effect of Citral on Aquaporin 5 and Trpv4 Expressions and Uterine Contraction in Rat—An Alternative Mechanism

Abstract

Aquaporins (AQPs) are expressed in the uterus, playing a physiological role during pregnancy. An osmotic pathway—through AQP5—may modify the transient potential vanilloid 4 (TRPV4) function and uterine contraction. Our aim was to determine the role of TRPV4 antagonist citral in the regulation of pregnant uterine contraction. In vitro uterine contractions were evoked by KCl and the response was modified with citral. The expressions of TRPV4 and AQP5 were measured by RT-PCR and Western blot techniques. The lengths of gestational periods were determined in normal and LPS-induced preterm births after citral treatment, in vivo. Citral significantly decreased the uterine contraction on day 22 of pregnancy. AQP5 expression significantly increased after citral incubation; however, TRPV4 expression did not show significant changes. After citral pretreatment, the gestational period was extended both in normal and LPS-induced preterm births. Our results suppose that the downregulation of AQP5 may initiate hypertonic stress, activating TRPV4 the uterine contraction on the last day of the gestational period. The putative cooperation between AQP5 and TRPV4 may open a novel target to treat or prevent preterm birth.

Effect of Lippia alba (Mill.) N.E. Brown Essential Oil on the Human Umbilical Artery

“…Seres-Bokor et al [ 38 ] suggested an alternative mechanism for the relaxing effect of citral on rat uterus. A 14 day treatment in vivo with this monoterpenoid induced an increase of aquaporin channel (AQP5) expression in uterine smooth muscle, reducing hypertonic stress activation on the transient receptor potential cation channel receptor type 4 (TRPV4).…”

Physiological Cooperation between Aquaporin 5 and TRPV4

“…Citral ((2E)-3,7-dimethylocta-2,6-dienal) is a bioactive component of lemongrass, a naturally occurring TRPV4 antagonist used to investigate the relationship between TRPV4 and AQP5 channels in the late-pregnant rat uterus [ 47 ]. It was found that AQP5 expression significantly increased, and TRPV4 expression did not change significantly after citral incubation in the 22-day pregnant rat uteri, in vitro.…”

“…The activation of TRPV4 leads to the Ca 2+ current, which in turn plays a role in myometrial contractions and thus in the induction of labor. The decrease in AQP5 expression on the day of delivery can be explained as a result of cell volume regulation [ 47 ].…”

“… Co-expression and cooperation of TRPV4 and AQP5 influence the contractions in the late-pregnant uterus [ 26 , 47 ]. The osmotic stress (through the AQP5) activated the TRPV4, and TRPV4 activation triggers Ca 2+ flow, which contributes to the creation of uterine contractions.…”