Nozu Tsukasa, Kumei Shima, Takakusaki Kaoru, Okumura Toshikatsu
Department of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan,
J Gastroenterol. 2014 May;49(5):799-805. doi: 10.1007/s00535-013-0828-8. Epub 2013 May 5.
Stress alters gastrointestinal motility through central and peripheral corticotropin-releasing factor (CRF) pathways. Accumulating evidence has demonstrated that peripheral CRF is deeply involved in the regulation of gastric motility, and enhances gastric contractions through CRF receptor type 1 (CRF1) and delays gastric emptying (GE) through CRF receptor type 2 (CRF2). Since little is known whether water-avoidance stress (WAS) alters gastric motility, the present study tried to clarify this question and the involvement of peripheral CRF receptor subtypes in the mechanisms.
We recorded intraluminal gastric pressure waves using a perfused manometric method. The rats were anesthetized and the manometric catheter was inserted into the stomach 4-6 days before the experiments. We assessed the area under the manometric trace as the motor index (MI), and compared this result with those obtained 1 h before and after initiation of WAS in nonfasted conscious rats. Solid GE for 1 h was also measured.
WAS significantly increased gastric contractions. Intraperitoneal (ip) administration of astressin (100 μg/kg, 5 min prior to stress), a nonselective CRF antagonist, blocked the response to WAS. On the other hand, pretreatment (5 min prior to stress) with neither astressin2-B (200 μg/kg, ip), a selective CRF2 antagonist, nor urocortin 2 (30 μg/kg, ip), a selective CRF2 agonist, modified the response to WAS. These drugs did not alter the basal MI. WAS did not change GE.
WAS may activate peripheral CRF1 but not CRF2 signaling and stimulates gastric contractions without altering GE.
应激通过中枢和外周促肾上腺皮质激素释放因子（CRF）途径改变胃肠动力。越来越多的证据表明，外周CRF深度参与胃动力的调节，通过1型CRF受体（CRF1）增强胃收缩，并通过2型CRF受体（CRF2）延迟胃排空（GE）。由于对水回避应激（WAS）是否改变胃动力知之甚少，本研究试图阐明这个问题以及外周CRF受体亚型在其中的作用机制。
我们使用灌注测压法记录胃腔内压力波。在实验前4 - 6天对大鼠进行麻醉并将测压导管插入胃中。我们将测压曲线下的面积评估为运动指数（MI），并将此结果与未禁食清醒大鼠WAS开始前1小时和开始后1小时获得的结果进行比较。还测量了1小时的固体GE。
WAS显著增加胃收缩。腹腔注射（ip）阿斯特辛（100μg/kg，应激前5分钟），一种非选择性CRF拮抗剂，可阻断对WAS的反应。另一方面，用选择性CRF2拮抗剂阿斯特辛2 - B（200μg/kg，ip）或选择性CRF2激动剂尿皮质素2（30μg/kg，ip）预处理（应激前5分钟）均未改变对WAS的反应。这些药物未改变基础MI。WAS未改变GE。
WAS可能激活外周CRF1而非CRF2信号传导，并刺激胃收缩而不改变GE。
