title: Molecular and functional characterization of TRPV4 channels in pregnant and nonpregnant mouse uterus.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
authors.forename: Vishakha
authors.initials: V
authors.lastname: Singh
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Ram
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
authors.forename: Kannan
authors.initials: K
authors.lastname: Kandasamy
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Thangamalai
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
authors.forename: Soumen
authors.initials: S
authors.lastname: Choudhary
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
authors.forename: Jeevan Ranjan
authors.initials: JR
authors.lastname: Dash
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India. Electronic address: subhaparida1210@gmail.com.
authors.forename: Subhashree
authors.initials: S
authors.lastname: Parida
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
authors.forename: Thakur Uttam
authors.initials: TU
authors.lastname: Singh
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, U.P., India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D007124:Immunoenzyme Techniques; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: C530602:N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide; D012333:RNA, Messenger; D013449:Sulfonamides; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D007930:Leucine
keywords: GSK1016790A; HC067047; Mouse uterus; PGF2α; TRPV4 channel