THE EFFECT OF 5-AMINOSALICYLATE AND PARA-AMINOSALICYLATE ON THE SYNTHESIS OF PROSTAGLANDIN E(2) AND LEUKOTRIENE B-4 IN ISOLATED COLONIC MUCOSAL CELLS

The effect of 5-aminosalicylate (5-ASA) and para-aminosalicylate (PAS) on the synthesis of prostaglandin E(2) (PGE(2)) and leukotriene B-4 ( LTB(4)) was studied in 24 healthy volunteers. Both drugs are successfu lly used in the treatment of chronic inflammatory bowel disease, but t he biochemical pathway of their anti-inflammatory action is still unkn own. Biopsies were taken from the descending colon and were isolated b iochemically. 5-ASA, PAS and a control were added to the suspension of isolated colonic mucosal cells and incubated over 0-45 min. Both 5-AS A and PAS did not alter the PGE(2) production but, compared with PAS a nd the control, 5-ASA decreased the LTB(4) synthesis in a dose-related fashion. As a result, the LTB(4)/PGE(2) ratio was significantly dimin ished by 10(-4) mol/l 5-ASA. These findings are consistent with those of other authors, indicating that 5-ASA, at least in part, modulates t he colonic eicosanoid synthesis. In contrast, PAS did not influence th e mucosal production of PGE(2) and LTB(4) and therefore must exert som e other biochemical action in order to explain its therapeutic effects in the treatment of Crohn's disease or ulcerative colitis.