A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats.

We previously reported that short-term immobilization stress of rats causes increased colonic mucin release, goblet cell depletion, prostaglandin E2 secretion, and colonic mast cell activation, as well as increased colonic motility. The purpose of this study was to investigate whether neurotensin (NT), a peptide expressed in both brain and digestive tract, participates in these responses. Rats were pretreated with SR 48692 (1 mg/kg, i.p.), an NT antagonist, 15 min before immobilization (30 min). The administration of the antagonist significantly inhibited stress-mediated secretion of colonic mucin, prostaglandin E2, and a product of rat mast cells, rat mast cell protease II (P < 0.05), but did not alter the increase in fecal pellet output caused by immobilization stress. Immobilization stress also resulted in a quantifiable decrease in the abundance of NT receptor mRNA in rat colon compared with that in colonic tissues from nonimmobilized rats as measured by densitometric analysis of in situ hybridization studies (P < 0.03). We conclude that the peptide NT is involved in colonic goblet cell release and mucosal mast cell activation after immobilization stress. IMAGES:

本团队此前已报道，对大鼠施加短期束缚应激可引发结肠黏液分泌增加、杯状细胞耗竭、前列腺素E2分泌异常以及结肠肥大细胞活化，同时伴随结肠动力增强。本研究旨在探究在脑与消化道均有表达的肽类物质神经降压素（neurotensin, NT）是否参与上述应激应答过程。实验前15分钟，对大鼠予以神经降压素拮抗剂SR 48692（1 mg/kg，腹腔注射，i.p.）预处理，随后施加30分钟束缚应激。该拮抗剂的给药可显著抑制应激介导的结肠黏液、前列腺素E2以及大鼠肥大细胞产物——大鼠肥大细胞蛋白酶II的分泌（P < 0.05），但未改变束缚应激引发的粪便粒数增加现象。通过原位杂交实验的光密度分析结果显示，与未施加束缚应激的大鼠结肠组织相比，束缚应激可使大鼠结肠内神经降压素受体mRNA的丰度出现可量化的降低（P < 0.03）。综上，本研究证实肽类物质NT参与了束缚应激后的结肠杯状细胞分泌及黏膜肥大细胞活化过程。图像：