Eutamene H, Theodorou V, Fioramonti J, Bueno L
Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
Gastroenterology. 1995 Aug;109(2):483-9. doi: 10.1016/0016-5085(95)90336-4.
BACKGROUND & AIMS: Interleukin (IL) 1 beta is known to induce a neurally mediated colonic water secretion in vivo. The aim of this study was to investigate the mechanism of action of IL-1 beta on colonic net water flux and the role of tachykinins and nitric oxide.
In anesthetized rats, isolated colonic loops were infused with Ringer's buffer containing [14C]polyethylene glycol 4000. Net water flux was calculated according to 14C activity determined in the effluent that was collected at 15-minute intervals.
Recombinant human IL-1 beta induced a 30-minute colonic hypersecretion. This effect was blocked by NK1 and NK2 antagonists, tetrodotoxin, and NG-methyl-L-arginine (L-NMA). L-arginine reversed the antisecretory effect of L-NMA on IL-1 beta-induced hypersecretion but did not modify the IL-1 beta-induced hypersecretion. Both NK1 and NK2 agonists induced a colonic hypersecretion, and their effects were blocked by L-NMA and tetrodotoxin. The NK3 agonist had no effect on water movements. The NK2 antagonist abolished the secretory effect of NK1 agonist; in contrast, the NK1 antagonist had no effect on the NK2 agonist-induced secretion.
IL-1 beta-induced colonic hypersecretion in vivo involves NK1- and NK2-receptor activation in cascade, suggesting a release of substance P and neurokinin A acting through NO release.
已知白细胞介素（IL）-1β可在体内诱导神经介导的结肠水分泌。本研究旨在探讨IL-1β对结肠净水通量的作用机制以及速激肽和一氧化氮的作用。
在麻醉大鼠中，向分离的结肠肠袢灌注含[14C]聚乙二醇4000的林格氏缓冲液。根据每隔15分钟收集的流出液中测定的14C活性计算净水通量。
重组人IL-1β诱导30分钟的结肠高分泌。此效应被NK1和NK2拮抗剂、河豚毒素及N-甲基-L-精氨酸（L-NMA）阻断。L-精氨酸逆转L-NMA对IL-1β诱导的高分泌的抗分泌作用，但不改变IL-1β诱导的高分泌。NK1和NK2激动剂均诱导结肠高分泌，且其效应被L-NMA和河豚毒素阻断。NK3激动剂对水转运无作用。NK2拮抗剂消除NK1激动剂的分泌效应；相反，NK1拮抗剂对NK2激动剂诱导的分泌无作用。
IL-1β在体内诱导的结肠高分泌涉及NK1和NK2受体的级联激活，提示P物质和神经激肽A通过一氧化氮释放发挥作用。
