Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Biopsies of colonic mucosa from patients with ulcerative colitis liberated more interleukin-1 beta, prostaglandin E2, leukotriene C4 and platelet-activating factor into the medium in which they were cultured than biopsies from patients with irritable bowel syndrome and histologically normal mucosa. 2. Addition of interleukin-1 stimulated release of greater quantities of all these inflammatory mediators, including interleukin-1 itself, from inflamed and normal mucosa. 3. Blockade of cyclo-oxygenase with indomethacin or of lipoxygenase with ICI 207968 or of phospholipase A2 with mepacrine inhibited release of prostaglandin E2 or leukotriene C4 or both of these plus platelet-activating factor, respectively. 4. Interleukin-1 stimulated the short-circuit current across isolated rat colonic mucosa mounted in flux chambers in a dose-dependent manner (Km 2 x 10(-11) mol/l). This stimulation was markedly inhibited by the removal of chloride from the bathing media. 5. Indomethacin or ICI 207968 inhibited the short-circuit current response to interleukin-1 and a combination of these antagonists produced a greater inhibition. Mepacrine caused an even greater inhibition whereas tetrodotoxin plus mepacrine inhibited the current completely. 6. These data indicate that interleukin-1, released in excess from inflamed colonic mucosa, stimulates the release of a range of inflammatory mediators as well as of more interleukin-1. It probably acts by stimulating phospholipase A2 in inflammatory cells, probably lymphocytes, and can do so in normal and inflamed mucosa. Since, in rat colonic mucosa it stimulated an electrical response in very low concentrations, it is feasible that it is involved in the chloride secretion, and hence the diarrhoea, which may occur in inflammatory reactions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potential role for interleukin-1 in the pathophysiology of ulcerative colitis. 803 15

The synthesis of cyclooxygenase (CO) and lipoxygenase (LO) metabolites of arachidonic acids, such as prostaglandins (PG) E2, F2 alpha, 6-keto-P1 alpha, thromboxane B2 (TB2), leukotriene B4 (LTB4) and hydroxyeicosatetraenic acids (HETEA) in the biopsy specimens of the colonic mucosa (CM) was studied in vitro in 30 patients aged 17-66 years who had ulcerative colitis (UC) of various severity and extent. The biopsy specimens of CM from 10 patients with the irritable bowel syndrome were used for comparison. A proportional severity of the disease and increased synthesis of CO and LO metabolites in CM was ascertained in a phase of UC. In the early phase of clinical remission (on the average, following 4 weeks of therapy), there was a comparative reduction in the level of eicosanoids with the preserved high production of TB2 and LO derivatives (LTB4 and HETEA). At the same time, in patients with severe UC, a higher synthesis of LTB4 and HETEA and PG was preserved. The predominance of CM production of eicosanoids having aggregative, vasoconstrictor, and proinflammatory effects (less coefficients of 6-keto-PGF1 alpha/TB2 and PG/LTB4 + ETEA), which had been detected in a phase of UC exacerbation, was preserved in a phase of remission development, by forming the metabolic basis for recurrence of the process.
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PMID:[Synthesis of eicosanoids in the colonic mucosa in patients with ulcerative colitis]. 1466 73