Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter

Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Shunsuke Takahashi, Mayumi Hirano, Kazuhiko Nakamura, Hirotada Akiho, Yoshinao Oda, Ryoichi Takayanagi

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

The lower esophageal sphincter (LES) plays an important role in coordinated esophageal motility. The present study aimed to elucidate how trypsin affects LES contractility. Porcine LES circular smooth muscle strips were prepared. Contractile responses to trypsin were assessed. Trypsin (300 nM) induced a transient contraction. At concentrations of 1 μM or higher, trypsin induced biphasic responses, consisting of a transient contraction followed by a transient relaxation. Pretreatment with either 1 μM tetrodotoxin or carbenoxolone had no effect on these responses. In contrast, trypsin-induced responses were completely blocked by pretreatment with the serine protease inhibitor. Pretreatment with 10 μM FSLLRY-NH2, a PAR2 antagonist, significantly inhibited trypsin-induced biphasic responses. Trypsin (1 μM)-induced contractions were partially inhibited by pretreatment with 10 μM Y-27632. In addition, trypsin (10 μM)-induced relaxation was partially inhibited by pretreatment with 10 μM Y-27632, 10 μM PD98059 or 10 μM SB203580. Trypsin-induced relaxation was abolished by increasing the extracellular K+ concentration to 40 mM, but not by pretreatment with l-arginine methyl ester. Furthermore, trypsin-induced relaxation was partially inhibited by pretreatment with 10 μM glibenclamide or 1 μM 4-aminopyridine. Trypsin causes biphasic regulation of LES tone by directly acting on smooth muscle. Rho-associated protein kinase (ROK) is involved in trypsin-induced contraction, whereas ROK, ERK1/2, p38MAPK, and membrane hyperpolarization are involved in relaxation. The regulation of LES tone by trypsin may play a role in esophageal motility.

元の言語英語
ページ(範囲)97-105
ページ数9
ジャーナルEuropean Journal of Pharmacology
752
DOI
出版物ステータス出版済み - 4 5 2015

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Lower Esophageal Sphincter
Trypsin
Swine
rho-Associated Kinases
Protein Kinases
Smooth Muscle
Carbenoxolone
4-Aminopyridine
Serine Proteinase Inhibitors
Glyburide
Tetrodotoxin

All Science Journal Classification (ASJC) codes

  • Pharmacology

これを引用

Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter. / Tanaka, Yoshimasa; Ihara, Eikichi; Hirano, Katsuya; Takahashi, Shunsuke; Hirano, Mayumi; Nakamura, Kazuhiko; Akiho, Hirotada; Oda, Yoshinao; Takayanagi, Ryoichi.

:: European Journal of Pharmacology, 巻 752, 05.04.2015, p. 97-105.

研究成果: ジャーナルへの寄稿記事

Tanaka, Yoshimasa ; Ihara, Eikichi ; Hirano, Katsuya ; Takahashi, Shunsuke ; Hirano, Mayumi ; Nakamura, Kazuhiko ; Akiho, Hirotada ; Oda, Yoshinao ; Takayanagi, Ryoichi. / Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter. :: European Journal of Pharmacology. 2015 ; 巻 752. pp. 97-105.
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abstract = "The lower esophageal sphincter (LES) plays an important role in coordinated esophageal motility. The present study aimed to elucidate how trypsin affects LES contractility. Porcine LES circular smooth muscle strips were prepared. Contractile responses to trypsin were assessed. Trypsin (300 nM) induced a transient contraction. At concentrations of 1 μM or higher, trypsin induced biphasic responses, consisting of a transient contraction followed by a transient relaxation. Pretreatment with either 1 μM tetrodotoxin or carbenoxolone had no effect on these responses. In contrast, trypsin-induced responses were completely blocked by pretreatment with the serine protease inhibitor. Pretreatment with 10 μM FSLLRY-NH2, a PAR2 antagonist, significantly inhibited trypsin-induced biphasic responses. Trypsin (1 μM)-induced contractions were partially inhibited by pretreatment with 10 μM Y-27632. In addition, trypsin (10 μM)-induced relaxation was partially inhibited by pretreatment with 10 μM Y-27632, 10 μM PD98059 or 10 μM SB203580. Trypsin-induced relaxation was abolished by increasing the extracellular K+ concentration to 40 mM, but not by pretreatment with l-arginine methyl ester. Furthermore, trypsin-induced relaxation was partially inhibited by pretreatment with 10 μM glibenclamide or 1 μM 4-aminopyridine. Trypsin causes biphasic regulation of LES tone by directly acting on smooth muscle. Rho-associated protein kinase (ROK) is involved in trypsin-induced contraction, whereas ROK, ERK1/2, p38MAPK, and membrane hyperpolarization are involved in relaxation. The regulation of LES tone by trypsin may play a role in esophageal motility.",
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AU - Ihara, Eikichi

AU - Hirano, Katsuya

AU - Takahashi, Shunsuke

AU - Hirano, Mayumi

AU - Nakamura, Kazuhiko

AU - Akiho, Hirotada

AU - Oda, Yoshinao

AU - Takayanagi, Ryoichi

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