Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body

Bai Xiaopeng, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Kayoko Nakano, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura

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Duodenal reflux of fluids containing trypsin relates to refractory gastroesophageal reflux disease (GERD). Esophageal peristalsis and clearance are important factors in GERD pathogenesis. However, the function of trypsin in esophageal body contractility is not fully understood. In this study, effects of trypsin on circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the porcine esophageal body were examined. Trypsin elicited a concentration dependent biphasic response, a major contraction and a subsequent relaxation only in CSM. In CSM, contraction occurred at trypsin concentrations of 100 nM and relaxation at 1 μM. A proteinase-activated receptor (PAR)2 activating peptide, SLIGKV-NH2(1 mM), induced a monophasic contraction. Those responses were unaffected by tetrodotoxin though abolished by the gap junction uncouplers carbenoxolone and octanol. They were also partially inhibited by a transient receptor potential vanilloid type 1 (TRPV1) antagonist and abolished by combination of neurokinin receptor 1 (NK1) and NK2antagonists, but not by an NK3antagonist, suggesting a PAR2-TRPV1-substance P pathway in sensory neurons. Substance P (100 nM), an agonist for various NK receptors (NK1, NK2and NK3) with differing affinities, induced significant contraction in CSM, but not in LSM. The contraction was also blocked by the combination of NK1and NK2antagonists, but not by the NK3antagonist. Moreover, substance P-induced contractions were unaffected by the TRPV1 antagonist, but inhibited by a gap junction uncoupler. In conclusion, trypsin induced a biphasic response only in CSM and this was mediated by PAR2, TRPV1 and NK1/2. Gap junctions were indispensable in this tachykinin-induced response.

元の言語英語
ページ(範囲)65-74
ページ数10
ジャーナルEuropean Journal of Pharmacology
797
DOI
出版物ステータス出版済み - 1 1 2017

All Science Journal Classification (ASJC) codes

  • Pharmacology

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