Urocortin 2 blocks the suppression of gastric antral contractions induced by lipopolysaccharide in freely moving conscious rats

Tsukasa Nozu , Kaoru Takakusaki , Toshikatsu Okumura
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引用次数: 3

Abstract

Lipopolysaccharide (LPS) inhibits gastric antral contractions in conscious rats. Since LPS regulates corticotropin-releasing factor type 2 receptor (CRF2) expression in the rat stomach, and activation of peripheral CRF2 alters gastric motility, we tried to determine the role of peripheral CRF2 in the LPS-induced suppression of gastric antral contractions. Intraluminal gastric pressure waves were measured in freely moving conscious non-fasted rats using the perfused manometric method. 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 intraperitoneal injection of drugs. LPS (0.2 mg/kg) significantly decreased MI. Indomethacin (10 mg/kg) itself did not alter MI but blocked this inhibitory action by LPS. Astressin 2-B (200 μg/kg), a selective CRF2 antagonist, modified neither the basal MI nor the action by LPS. Meanwhile, urocortin 2 (30 μg/kg), a selective CRF2 agonist, reversed the suppression by LPS without affecting the basal MI. This action by urocortin 2 was blocked by pretreatment with astressin 2-B. In conclusion, LPS inhibited gastric antral contractions possibly through a prostaglandin-dependent pathway. Peripheral CRF2 stimulation reversed this response by LPS.

尿皮质素2阻断脂多糖对自由运动大鼠胃窦收缩的抑制作用
脂多糖(LPS)抑制清醒大鼠胃窦收缩。由于LPS调节促肾上腺皮质激素释放因子2型受体(CRF2)在大鼠胃中的表达,而外周CRF2的激活会改变胃的运动,我们试图确定外周CRF2在LPS诱导的胃窦收缩抑制中的作用。用灌注测压法测量了自由运动清醒非禁食大鼠的胃腔内压力波。我们将测压痕迹下的面积作为运动指数(MI),并将此结果与腹腔注射药物前后1 h的结果进行比较。LPS (0.2 mg/kg)显著降低心肌梗死,吲哚美辛(10 mg/kg)本身不改变心肌梗死,但阻断了LPS的抑制作用。选择性CRF2拮抗剂Astressin 2-B (200 μg/kg)既不能改变基础心肌梗死,也不能改变LPS的作用。同时,选择性CRF2激动剂尿皮质素2 (30 μg/kg)可逆转LPS对CRF2的抑制作用,但不影响基础心肌梗死。尿皮质素2的这种作用可被应激素2- b预处理阻断。综上所述,LPS可能通过前列腺素依赖途径抑制胃窦收缩。外周CRF2刺激通过LPS逆转了这种反应。
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来源期刊
Regulatory Peptides
Regulatory Peptides 医学-内分泌学与代谢
自引率
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审稿时长
2 months
期刊介绍: Regulatory Peptides provides a medium for the rapid publication of interdisciplinary studies on the physiology and pathology of peptides of the gut, endocrine and nervous systems which regulate cell or tissue function. Articles emphasizing these objectives may be based on either fundamental or clinical observations obtained through the disciplines of morphology, cytochemistry, biochemistry, physiology, pathology, pharmacology or psychology.
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