教員業績データベース |
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論文種別 | 総説 |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASICs sensitization in human esophageal epithelial cells. |
掲載誌名 | 正式名:American journal of physiology. Gastrointestinal and liver physiology 略 称:Am J Physiol Gastrointest Liver Physiol ISSNコード:1522-1547(Electronic)0193-1857(Linking) |
巻・号・頁 | 309(8),pp.695-702 |
著者・共著者 | Wu Liping, Oshima Tadayuki, Shan Jing, Sei Hiroo, Tomita Toshihiko, Ohda Yoshio, Fukui Hirokazu, Watari Jiro, Miwa Hiroto |
発行年月 | 2015/08 |
概要 | UNASSIGNED:Esophageal visceral hypersensitivity has been proposed to be the pathogenesis of heartburn sensation in non-erosive reflux disease. Protease-activated receptor-2 (PAR-2) is expressed in human esophageal epithelial cells, and is believed to play a role in inflammation and sensation. PAR-2 activation may modulate these responses through adenosine triphosphate (ATP) release, which is involved in transduction of sensation and pain. The transient receptorUNASSIGNED:potential vanilloid receptor 1 (TRPV1) and acid-sensing ion channels (ASICs) are both acid-sensitive nociceptors. However, the interaction among these molecules and the mechanisms of heartburn sensation are still not clear. We therefore examined whether ATP release in human esophageal epithelial cells in response to acid is modulated by TRPV1 and ASICs and whether PAR-2 activation influences the sensitivity of TRPV1 and ASICs. Weak acid (pH 5) stimulated the release of ATP from primary human esophageal epithelial cells (HEECs). This effect was significantly reduced after pretreatment with 5-iodoresiniferatoxin (IRTX), a TRPV1 specific antagonist or with amiloride, a non-selective ASIC blocker. TRPV1 and ASIC3 small interfering RNA (siRNA) transfection also decreased weak acid-induced ATP release. Pretreatment of HEECs with trypsin, tryptase or a PAR-2 agonist enhanced weak acid-induced ATP release. Trypsin treatment led to the phosphorylation of TRPV1. Acid-induced ATP release enhancement by trypsin was partially blocked by IRTX, amiloride or a PAR2 antagonist. Conversely, acid-induced ATP release was augmented by PAR-2 activation through TRPV1 and ASICs. These findings suggested that the pathophysiology of heartburn sensation or esophageal hypersensitivity may be associated with the activation of PAR-2, TRPV1 and ASICs. |
DOI | 10.1152/ajpgi.00162.2015 |
PMID | 26294672 |