title: Arachidonic acid metabolism and intracellular calcium concentration in inflammatory bowel disease.
abstract: OBJECTIVE
  To study the alteration of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) synthesis and intracellular Ca2+ concentration in chronic inflammatory bowel disease, and to ascertain the effect of anti-inflammatory drugs and other mediators on eicosanoid synthesis and Ca2+ concentration.
  
  
  METHODS
  Biopsies taken from the descending colon were isolated biochemically. The suspension of isolated mucosal cells was incubated for 15 min in the presence and absence of arachidonic acid and the Ca2+ ionophore A23187. PGE2 and LTB4 concentrations in the incubation medium were measured by radioimmunoassay, and the intracellular Ca2+ concentration was determined using fura-2. We studied 107 subjects. In addition, the effects of bradykinin, endothelin, cyclosporin A and PGE2 on intracellular Ca2+ concentration were determined in 25 individuals.
  
  
  RESULTS
  Untreated patients with active inflammatory bowel disease showed a significant increase in LTB4 synthesis compared with healthy controls. However, in patients receiving steroids, sulphasalazine or 5-aminosalicylic acid, both LTB4 and PGE2 synthesis were markedly decreased. When arachidonic acid was added to the cell suspension, it significantly stimulated LTB4 synthesis, especially in patients with active disease. Patients with active Crohn's disease or ulcerative colitis had moderately higher Ca2+ levels than healthy controls. However, there was a significant decrease in intracellular Ca2+ concentration in patients with quiescent disease who were receiving maintenance therapy.
  
  
  CONCLUSIONS
  We suggest that increased LTB4 synthesis and elevated intracellular Ca2+ concentrations contribute to the pathophysiology of inflammatory bowel disease. Drugs effective in the treatment of these diseases may exert their pharmacological action by normalizing these pathological findings.
authors.affiliation: Medical Policlinic, University of Bonn, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schmidt
authors.forename: E
authors.initials: E
authors.lastname: Kosché
authors.forename: B
authors.initials: B
authors.lastname: Baumeister
authors.forename: H
authors.initials: H
authors.lastname: Vetter
mesh_terms: D000636:Aminosalicylic Acids / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000493:pharmacokinetics*; D001706:Biopsy; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007424:Intracellular Fluid / Q000378:metabolism*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D019804:Mesalamine; D011863:Radioimmunoassay; D013256:Steroids / Q000627:therapeutic use; D012460:Sulfasalazine / Q000627:therapeutic use
chemical_list: D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013256:Steroids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D012460:Sulfasalazine; D019804:Mesalamine; D015232:Dinoprostone; D002118:Calcium