A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats
A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats
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DOI：
10.1073/pnas.93.22.12611
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发表时间：
1996-10-29
影响因子：
11.1
通讯作者：
Pothoulakis, C
中科院分区：
文献类型：
--
作者：
Castagliuolo, I;Leeman, SE;Pothoulakis, C
我们之前报道过，大鼠的短期固定应激会导致结肠粘蛋白释放增加、杯状细胞耗竭、前列腺素 E(2) 分泌和结肠肥大细胞激活以及结肠运动增加。本研究的目的是调查神经降压素 (NT)（一种在大脑和消化道中表达的肽）是否参与这些反应。在固定前 15 分钟（30 分钟），用 NT 拮抗剂 SR 48692（1 mg/kg，腹腔注射）对大鼠进行预处理。施用拮抗剂显着抑制应激介导的结肠粘蛋白、前列腺素E(2)和大鼠肥大细胞的产物、大鼠肥大细胞蛋白酶II的分泌(P < 0.05)，但不改变由固定应激引起的粪便颗粒输出的增加。通过原位杂交研究的光密度分析测量，与非固定大鼠结肠组织相比，固定应激还导致大鼠结肠中 NT 受体 mRNA 丰度可量化降低（P < 0.03）。我们得出结论，肽 NT 参与固定应激后结肠杯状细胞释放和粘膜肥大细胞激活。
We previously reported that short-term immobilization stress of rats causes increased colonic mucin release, goblet cell depletion, prostaglandin E(2) 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 E(2), 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.