Molecular mechanism of luminal pressure reception and ATP release in gastrointestinal epithelium

Approximately 15% of Japanese people have chronic abdominal pain of unknown origin and hypersensitivity to gastrointestinal pressure is one of possible causes. The esophagus senses a tension with mechano-sensitive TRPV4 ion channel and releases bag-like adenosine triphosphate (ATP) using its transporter (VNUT). As a result of the study, TRPV4 and VNUT are present not only in the esophagus but also from the stomach to the rectum, and ATP is released via VNUT by TRPV4 stimulation, including stretch stimuli. Mice lacking TRPV4 have gastric motor abnormality and Helicobacter pylori infection decreases TRPV4 (gene methylation). It has also succeeded in quantifying the TRPV4 stimulating component synthesized in the gastrointestinal tract and so the possibility of quantifying invisible abdominal pain has come out.