Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
Life Sci. 2015 Feb 1;122:51-8. doi: 10.1016/j.lfs.2014.12.010. Epub 2014 Dec 19.
The aim of the present study was to characterize TRPV4 channels in pregnant and nonpregnant mouse uterus and examine their functional role in spontaneous and agonist-induced contractions.
We used RT-PCR, Western blot and immunohistochemistry experiments to demonstrate the presence of TRPV4 mRNA and protein, respectively in both pregnant and nonpregnant mouse uterus. Tension experiments were conducted for functional characterization of the TRPV4 channels.
TRPV4 mRNA and protein were detected in both pregnant and nonpregnant mouse uterus with distribution in both endometrium and myometrium. The TRPV4 channel agonist GSK1016790A (GSK) increased myometrial contraction in pregnant (Emax 336.8±21.35%; pD2 7.79±0.29) and nonpregnant (Emax 238±28.13%; pD2 7.61±0.57) animals. HC067047 (1μM), a selective blocker of the TRPV4 channel, antagonized the contractions to GSK in pregnant (Emax 171±18.26%; pD2 6.58±0.37) and nonpregnant (Emax 78.12±9.32%; pD2 7.54±0.9) uteri. Further, HC067047 (1μM) inhibited contractions induced by PGF2α in the pregnant (Emax 183.2±13.94%; pD2 7.01±0.30 versus control Emax 495.7±42.49%; pD2 7.12±0.24) and nonpregnant (Emax 105.3±7.10%; pD2 7.24±0.34 versus control Emax 232.5±12.27%; pD2 7.83±0.29) uteri.
TRPV4 channels are present in the pregnant and nonpregnant mouse uteri, and their activation by endogenous ligands like prostaglandin increases myometrial contractility. Thus, the TRPV4 channel can be an important target in reducing myometrial contractility in preterm labor.
本研究旨在研究 TRPV4 通道在妊娠和非妊娠小鼠子宫中的特征，并探讨其在自发性和激动剂诱导收缩中的功能作用。
我们使用 RT-PCR、Western blot 和免疫组织化学实验分别证明了 TRPV4 mRNA 和蛋白在妊娠和非妊娠小鼠子宫中的存在。张力实验用于 TRPV4 通道的功能特征分析。
TRPV4 mRNA 和蛋白在妊娠和非妊娠小鼠子宫中均有检测到，分布于子宫内膜和子宫肌层。TRPV4 通道激动剂 GSK1016790A（GSK）增加了妊娠（Emax 336.8±21.35%；pD2 7.79±0.29）和非妊娠（Emax 238±28.13%；pD2 7.61±0.57）动物的子宫收缩。选择性 TRPV4 通道阻滞剂 HC067047（1μM）拮抗了 GSK 对妊娠（Emax 171±18.26%；pD2 6.58±0.37）和非妊娠（Emax 78.12±9.32%；pD2 7.54±0.9）子宫收缩的作用。此外，HC067047（1μM）抑制了妊娠（Emax 183.2±13.94%；pD2 7.01±0.30 与对照 Emax 495.7±42.49%；pD2 7.12±0.24）和非妊娠（Emax 105.3±7.10%；pD2 7.24±0.34 与对照 Emax 232.5±12.27%；pD2 7.83±0.29）子宫中由 PGF2α 诱导的收缩。
TRPV4 通道存在于妊娠和非妊娠的小鼠子宫中，其被内源性配体如前列腺素激活后可增加子宫肌层的收缩性。因此，TRPV4 通道可能是减少早产子宫收缩的重要靶点。
