leukotriene-c4 and Diarrhea

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 Magnus 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 concentrations (1 nM-100 nM). 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 peptidoleukotrienes. 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.

Topics: Adult; Animals; Biological Transport; Chromones; Colon; Diarrhea; Electric Conductivity; Humans; In Vitro Techniques; Intestinal Mucosa; Leukotriene Antagonists; Leukotriene C4; Leukotriene D4; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Rats; Rats, Wistar

The capacity of the small intestinal mucosa to generate leukotriene B4 (LTB4) and C4 (LTC4) in children with coeliac disease (CD) was investigated by measuring the production of LTB4 and LTC4 in intestinal biopsy specimens after stimulation with 10 microM calcium ionophore A23187. In addition, we examined the relationship between the production of LTB4 and LTC4 in the small intestinal mucosa and symptoms of diarrhoea. LTB4 and LTC4 production was significantly higher in biopsies from patients with active CD than from controls (p < 0.05 and p < 0.01, respectively). There was no significant difference in LTB4 and LTC4 production between patients with inactive CD and controls. In both patients with active CD and controls, no difference in LTB4 and LTC4 production was observed between the patients with and without diarrhoea. These findings suggest that enhanced generation of LTB4 and LTC4 in the small intestinal mucosa may contribute to the pathophysiology of CD but would not be related to the development of diarrhoea.

Topics: Calcimycin; Celiac Disease; Child; Child, Preschool; Data Interpretation, Statistical; Diarrhea; Humans; In Vitro Techniques; Infant; Intestinal Mucosa; Intestine, Small; Leukotriene B4; Leukotriene C4; Radioimmunoassay