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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Transient receptor potential vanilloid 4-dependent calcium influx and ATP release in mouse and rat gastric epithelia
Hiroshi Mihara, Nobuhiro Suzuki, Ammar Abdullkader Boudaka, Jibran Sualeh Muhammad, Makoto Tominaga, Yoshiaki Tabuchi, Toshiro Sugiyama
Hiroshi Mihara, Nobuhiro Suzuki, Jibran Sualeh Muhammad, Toshiro Sugiyama, Department of Gastroenterology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
Hiroshi Mihara, Ammar Abdullkader Boudaka, Makoto Tominaga, Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki 444-8787, Japan
Ammar Abdullkader Boudaka, Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Sultanate of Oman
Yoshiaki Tabuchi, Life Science Research Center, University of Toyama, Toyama 930-0194, Japan
Author contributions: Mihara H and Sugiyama T designed study concept; Mihara H, Suzuki N, Boudaka AA, Muhammad JS and Tabuchi Y acquired data; Mihara H and Suzuki N analyzed Data; Mihara H, Suzuki N, Tominaga M and Sugiyama T contributed to data interpretation; Mihara H drafted the manuscript; and all authors critically revised the manuscript.
Supported by Grants from the University of Toyama and JSPS KAKENHI to Mihara H, No. 26870214.
Institutional animal care and use committee statement: All procedures involving the care and use of animals were approved by The Institutional Animal Care and Use Committee of the National Institutes of Natural Sciences.
Conflict-of-interest statement: No conflict of interest exists.
Data sharing statement: There are no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hiroshi Mihara, MD, PhD, Assistant Professor, Department of Gastroenterology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. m164-tym@umin.net
Telephone: +81-76-4347301 Fax: +81-76-4345072
Received: February 16, 2016
Peer-review started: February 17, 2016
First decision: March 31, 2016
Revised: April 11, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: June 28, 2016
AIM: To explore the expression of transient receptor potential vanilloid 4 (TRPV4) and its physiological meaning in mouse and rat gastric epithelia.
METHODS: RT-PCR and immunochemistry were used to detect TRPV4 mRNA and protein expression in mouse stomach and a rat normal gastric epithelial cell line (RGE1-01), while Ca2+-imaging and electrophysiology were used to evaluate TRPV4 channel activity. ATP release was measured by a luciferin-luciferase assay. Gastric emptying was also compared between WT and TRPV4 knockout mice.
RESULTS: TRPV4 mRNA and protein were detected in mouse tissues and RGE1-01 cells. A TRPV4-specific agonist (GSK1016790A) increased intracellular Ca2+ concentrations and/or evoked TRPV4-like current activities in WT mouse gastric epithelial cells and RGE1-01 cells, but not TRPV4KO cells. GSK1016790A or mechanical stimuli induced ATP release from RGE1-01 cells while TRPV4 knockout mice displayed delayed gastric emptying in vivo.
CONCLUSION: TRPV4 is expressed in mouse and rat gastric epithelium and contributes to ATP release and gastric emptying.
Core tip: A mechano-sensitive ion channel, transient receptor potential vanilloid 4 (TRPV4), is expressed in gastric epithelium and contributes to ATP release and gastric emptying. These findings suggest that gastric distension stimulates TRPV4 on gastric epithelium and released ATP stimulates sub-epithelial nerve fibers or acts on visceral smooth muscles. TRPV4 might be a promising novel diagnostic and therapeutic target for functional gastric disorders.
