Abstract:
Motilin is an important hormonal regulator in the migrating motor complex (MMC). Free fatty acid receptor-1 (FFAR1, also known as GPR40) has been reported to stimulate motilin release in human duodenal organoids. However, how FFAR1 regulates gastric motility in vivo is unclear. This study investigated the role of FFAR1 in the regulation of gastric contractions and its possible mechanism of action using Suncus murinus. Firstly, intragastric administration of oleic acid (C18:1, OA), a natural ligand for FFAR1, stimulated phase II-like contractions, followed by phase III-like contractions in the fasted state, and the gastric emptying rate was accelerated. The administration of GW1100, an FFAR1 antagonist, inhibited the effects of OA-induced gastric contractions. Intravenous infusion of a ghrelin receptor antagonist (DLS) or serotonin 4 (5-HT4) receptor antagonist (GR125487) inhibited phase II-like contractions and prolonged the onset of phase III-like contractions induced by OA. MA-2029, a motilin receptor antagonist, delayed the occurrence of phase III-like contractions. In vagotomized suncus, OA did not induce phase II-like contractions. In addition, OA promoted gastric emptying through a vagal pathway during the postprandial period. However, OA did not directly act on the gastric body to induce contractions in vitro. In summary, this study indicates that ghrelin, motilin, 5-HT, and the vagus nerve are involved in the role of FFAR1 regulating MMC. Our findings provide novel evidence for the involvement of nutritional factors in the regulation of gastric motility.
摘要:
胃动素是迁移运动复合体(MMC)中重要的激素调节剂。已经报道游离脂肪酸受体-1(FFAR1,也称为GPR40)刺激人十二指肠类器官中的胃动素释放。然而,目前尚不清楚FFAR1在体内如何调节胃运动.本研究使用Suncusmurinus研究了FFAR1在胃收缩调节中的作用及其可能的作用机制。首先,油酸(C18:1,OA)的胃内给药,FFAR1的天然配体,刺激II期样收缩,随后是禁食状态下的III期类似收缩,胃排空速度加快。给予GW1100,一种FFAR1拮抗剂,抑制OA诱导的胃收缩的作用。静脉输注生长素释放肽受体拮抗剂(DLS)或5-羟色胺4(5-HT4)受体拮抗剂(GR125487)抑制了II期样收缩,并延长了OA诱导的III期样收缩的发作。MA-2029,一种胃动素受体拮抗剂,延迟III期样收缩的发生。在阴道切除的太阳树中,OA没有诱导II期样收缩。此外,OA在餐后期间通过迷走神经途径促进胃排空。然而,OA在体外不直接作用于胃体以诱导收缩。总之,这项研究表明ghrelin,胃动素,5-HT,迷走神经参与FFAR1调节MMC的作用。我们的发现为营养因素参与胃动力调节提供了新的证据。