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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)65-74
Number of pages10
JournalEuropean Journal of Pharmacology
Volume797
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Muscle Relaxation
Muscle Contraction
Trypsin
Smooth Muscle
Swine
PAR-2 Receptor
Gap Junctions
Substance P
Neurokinin-1 Receptors
Gastroesophageal Reflux
Carbenoxolone
Duodenogastric Reflux
Octanols
Tachykinins
Peristalsis
Tetrodotoxin
Sensory Receptor Cells
vanilloid receptor subtype 1
Peptides

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body. / Xiaopeng, Bai; Tanaka, Yoshimasa; Ihara, Eikichi; Hirano, Katsuya; Nakano, Kayoko; Hirano, Mayumi; Oda, Yoshinao; Nakamura, Kazuhiko.

In: European Journal of Pharmacology, Vol. 797, 01.01.2017, p. 65-74.

Research output: Contribution to journalArticle

@article{ca247426bec34285baae3c8d139d5cb5,
title = "Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body",
abstract = "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.",
author = "Bai Xiaopeng and Yoshimasa Tanaka and Eikichi Ihara and Katsuya Hirano and Kayoko Nakano and Mayumi Hirano and Yoshinao Oda and Kazuhiko Nakamura",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.ejphar.2017.01.004",
language = "English",
volume = "797",
pages = "65--74",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

TY - JOUR

T1 - Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body

AU - Xiaopeng, Bai

AU - Tanaka, Yoshimasa

AU - Ihara, Eikichi

AU - Hirano, Katsuya

AU - Nakano, Kayoko

AU - Hirano, Mayumi

AU - Oda, Yoshinao

AU - Nakamura, Kazuhiko

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85009998052&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009998052&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2017.01.004

DO - 10.1016/j.ejphar.2017.01.004

M3 - Article

C2 - 28088386

AN - SCOPUS:85009998052

VL - 797

SP - 65

EP - 74

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -