The effect of 5-aminosalicylate and para-aminosalicylate on the synthesis of prostaglandin E2 and leukotriene B4 in isolated colonic mucosal cells.
The effect of 5-aminosalicylate (5-ASA) and para-aminosalicylate (PAS) on the synthesis of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) was studied in 24 healthy volunteers. Both drugs are successfully used in the treatment of chronic inflammatory bowel disease, but the biochemical pathway of their anti-inflammatory action is still unknown. Biopsies were taken from the descending colon and were isolated biochemically. 5-ASA, PAS and a control were added to the suspension of isolated colonic mucosal cells and incubated over 0-45 min. Both 5-ASA and PAS did not alter the PGE2 production but, compared with PAS and the control, 5-ASA decreased the LTB4 synthesis in a dose-related fashion. As a result, the LTB4/PGE2 ratio was significantly diminished 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 the colonic eicosanoid synthesis. In contrast, PAS did not influence the mucosal production of PGE2 and LTB4 and therefore must exert some other biochemical action in order to explain its therapeutic effects in the treatment of Crohn's disease or ulcerative colitis.
Schmidt
C
C
Medical Poliklinik, University of Bonn, Germany.
Fels
T
T
Baumeister
B
B
Vetter
H
H
D000328:Adult; D000368:Aged; D010131:Aminosalicylic Acid / Q000494:pharmacology*; D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D019804:Mesalamine; D008875:Middle Aged
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007975:Leukotriene B4; D019804:Mesalamine; D010131:Aminosalicylic Acid; D015232:Dinoprostone