Effects of leukotrienes on ion transport in human calonic mucosa

白三烯在炎症性肠病中起重要作用。先前的研究已经揭示了肽白细胞三烯对平滑肌收缩和跨粘膜离子转运的影响，这可能导致肠运动过度以及电解质和水的损失，即，本研究的目的是评价肽白细胞三烯拮抗剂ONO-1078的作用，并评估其未来可能的临床应用。我们研究了ONO-1078对肽白三烯诱导的大鼠结肠电解质转运和肌肉收缩变化的影响，采用Ussing和Mugnus技术。在结肠镜检查中获得的人类活检标本也用于离子转运研究。在大鼠和人类中的钙离子转运，以及大鼠结肠中的平滑肌收缩，由估计的间质浓度（1 nM-100 nM）的相似剂量的肽白细胞三烯诱导。实验结果表明，短电流的变化有两个阶段，一个是短暂的下降，另一个是短暂的上升，这两个阶段的变化主要是由Na^+和Cl_-引起的.肽白细胞三烯引起大鼠结肠平滑肌的短暂收缩，这种作用可能与炎症性肠病的腹泻有关，ONO-1078可抑制肽白细胞三烯的这种作用. ONO-1078有望在临床应用中有效对抗轻度至中度炎症性肠病中的肽白三烯相关腹泻。

Leukotrienes play important roles in inflammatory bowel diseases. Previous studies have revealed the effects of peptidoleukotrienes on smooth muscle contraction and transmucosal ion transport, which may cause hyperactive bowel movement and the loss of electrolytes and water, i.e., diarrhea.The purpose of the present study was to evaluate the effects of the peptidoleukotrienes antagonist ONO-1078 and to assess its possible future clinical use. We examined the effects of ONO-1078 on peptidoleukotrienes-induced changes in electrolyte transport and muscle contraction in the rat colon, with the Ussing and Mugnus techniques. Human biopsy specimens obtained at colonoscopy were also used for ion transport studies. Transmucosal ion transport in both rats and humans, and smooth muscle contractions in the rat colon, were induced by similar doses of peptidoleukotrienes at estimated interstitial concentration (1nM-100nM). The time course of changes in short circuit current had two phases, a rapid and transient decrease and a subsequent transient increase, which seemed to be due mainly to Na^+ and Cl_-, respectively.Rat colon smooth muscle contracted transiently after the addition of peptidoleukotorienes.These effects of peptidoleukotrienes, which could be related to the diarrhea in inflammatory bowel diseases, were inhibited by ONO-1078. ONO-1078 is expected to be effective in clinical use against peptidoleukotrienes-related diarrhea in mild to moderate inflammatory bowel diseases.