Involvement of different receptor subtypes in prostaglandin e2-induced contraction and relaxation in the lower esophageal sphincter and esophageal body.
Involvement of different receptor subtypes in prostaglandin e2-induced contraction and relaxation in the lower esophageal sphincter and esophageal body.
复制标题
不同受体亚型参与前列腺素 e2 诱导的食管下括约肌和食管体的收缩和舒张。
DOI：
10.1016/j.ejphar.2019.172405
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发表时间：
2019
期刊：
影响因子：
5
通讯作者：
Ogawa Y
中科院分区：
文献类型：
--
作者：
Bai X;Ihara E;Otsuka Y;Tsuruta S;Hirano K;Tanaka Y;Ogino H;Hirano M;Chinen T;Akiho H;Nakamura K;Oda Y;Ogawa Y
前列腺素 E2 (PGE2) 在胃食管反流病 (GERD) 的发病机制中发挥作用。 PGE2 有 4 种亚型：PGE2 受体 1、2、3 和 4 (EP 1-4)。在GERD专利中，PGE2、EP2和EP4被上调。然而，PGE2对食管运动的影响仍然难以捉摸。我们研究了PGE2如何在器官浴中调节猪下食管括约肌（LES）的环形平滑肌以及食管体的环形和纵向平滑肌的运动。PGE2引起LES和环形平滑肌的紧张性松弛，但纵向平滑肌的短暂收缩。 LES 和环形平滑肌的松弛在模式和机制上相似，但 LES 的松弛程度要大得多。这种松弛被电压门控 K+ 通道阻断剂或 40mM K+ 去极化完全阻断，表明 K+ 通道的参与。纵向平滑肌收缩被L型Ca2+通道阻滞剂完全阻断，显示了Ca2+运动的贡献。用选择性受体激动剂和拮抗剂检查EP受体在运动中的参与。 EP2 和 EP4 的激活导致 LES 和环形平滑肌松弛。与 PGE2、EP2 和 EP4 激动剂相容，使 LES 比圆形平滑肌更显着松弛。 EP1促进纵向平滑肌收缩。PGE2在LES中的不同作用，环行和纵向平滑肌有助于食管运动，它们的损伤可能会增加食管反流的数量和频率。
Prostaglandin E2(PGE2) plays a role in the pathogenesis of gastro-esophageal reflux disease (GERD). There are 4 subtypes of PGE2, PGE2receptor 1, 2, 3 and 4 (EP 1–4). In GERD patents, PGE2, EP2 and EP4 are upregulated. However, the effects of PGE2 on esophageal motility remain elusive.We examined how PGE2regulates motility in the porcine circular smooth muscle of the lower esophageal sphincter (LES), and the circular and longitudinal smooth muscle of the esophagus body in organ bath.PGE2induced tonic relaxation in the LES and circular smooth muscle, but transient contraction in longitudinal smooth muscle. The relaxation of the LES and circular smooth muscle was similar in pattern and mechanism, but was much larger in the LES. The relaxation was completely blocked by a voltage-gated K+channel blocker or 40 mM K+depolarization, indicating the involvement of K+channel. Longitudinal smooth muscle contraction was completely blocked by an L-type Ca2+channel blocker, showing the contribution of Ca2+movement. The involvement of the EP receptor in motility was examined with selective receptor agonists and antagonists. Activation of EP2 and EP4 caused relaxation in the LES and circular smooth muscle. Compatible with PGE2, EP2 and EP4 agonists caused more significant relaxation in the LES than in circular smooth muscle. EP1 contributed to the longitudinal smooth muscle contraction.The different effects of PGE2in the LES, circular and longitudinal smooth muscle contributes to esophageal motility, their impairment might increase the amount and frequency of esophageal reflux.