Nozu Tsukasa, Takakusaki Kaoru, Okumura Toshikatsu
Department of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Research Center for Brain Function and Medical Engineering, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Regul Pept. 2014 May;190-191:12-7. doi: 10.1016/j.regpep.2014.04.004. Epub 2014 May 2.
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 1h 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.
脂多糖（LPS）可抑制清醒大鼠的胃窦收缩。由于LPS可调节大鼠胃中促肾上腺皮质激素释放因子2型受体（CRF2）的表达，且外周CRF2的激活会改变胃动力，因此我们试图确定外周CRF2在LPS诱导的胃窦收缩抑制中的作用。使用灌注测压法在自由活动的清醒非禁食大鼠中测量胃腔内压力波。我们将测压曲线下的面积评估为运动指数（MI），并将该结果与腹腔注射药物前后1小时获得的结果进行比较。LPS（0.2mg/kg）显著降低MI。吲哚美辛（10mg/kg）本身不会改变MI，但可阻断LPS的这种抑制作用。选择性CRF2拮抗剂Astressin 2-B（200μg/kg）既不改变基础MI，也不改变LPS的作用。同时，选择性CRF2激动剂尿皮质素2（30μg/kg）可逆转LPS的抑制作用，而不影响基础MI。尿皮质素2的这种作用可被Astressin 2-B预处理阻断。总之，LPS可能通过前列腺素依赖性途径抑制胃窦收缩。外周CRF2刺激可逆转LPS的这种反应。
