Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter.
Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter.
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胰蛋白酶诱导的猪下食管括约肌张力的双相调节。
DOI：
10.1016/j.ejphar.2015.02.008
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发表时间：
2015
影响因子：
5
通讯作者：
Takayanagi R
中科院分区：
文献类型：
--
作者：
Tanaka Y;Ihara E;Hirano K;Takahashi S;Hirano M;Nakamura K;Akiho H;Oda Y;Takayanagi R
食管下括约肌（LES）在协调食管运动中起着重要作用。本研究旨在阐明胰蛋白酶如何影响LES收缩性。制备猪LES环形平滑肌条。评估对胰蛋白酶的收缩反应。胰蛋白酶（300 nM）诱导短暂收缩。在1 μM或更高浓度下，胰蛋白酶诱导双相反应，包括短暂收缩和随后的短暂舒张。用1 μM河豚毒素或甘珀酸预处理对这些反应没有影响。与此相反，胰蛋白酶诱导的反应完全阻断预处理与丝氨酸蛋白酶抑制剂。PAR 2拮抗剂FSLLRY-NH 2（10 μM）预处理可显著抑制胰蛋白酶诱导的双相反应。用10 μM Y-27632预处理可部分抑制胰蛋白酶（1 μM）诱导的收缩。此外，用10 μM Y-27632、10 μM PD 98059或10 μM SB 203580预处理可部分抑制胰蛋白酶（10 μM）诱导的舒张。胰蛋白酶诱导的松弛被取消增加细胞外K+浓度为40 mM，但不是通过预处理与l-精氨酸甲酯。此外，10 μM格列本脲或1 μM 4-氨基吡啶预处理可部分抑制胰蛋白酶诱导的舒张。胰蛋白酶通过直接作用于平滑肌引起LES张力的双相调节。Rho相关蛋白激酶（ROK）参与胰蛋白酶诱导的收缩，而ROK、ERK 1/2、p38 MAPK和膜超极化参与舒张。胰蛋白酶对LES张力的调节可能在食管运动中起作用。
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 PAR2antagonist, 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 withl-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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