The effects of aminosalicylic acid derivatives on nitric oxide in a cell-free system.
OBJECTIVE
To determine the effect of aminosalicylic acid derivatives on the concentration of nitric oxide produced in a cell-free system, by the use of a sensitive and specific polarographic meter.


RESULTS
The aminosalicylic acid derivatives 3-ASA (IC50 100 microM), 4-ASA (IC50 350 microM) and 5-ASA (IC50 5 microM) all decreased the nitric oxide signal. These drugs had a similar inhibitory effect on the formation in vitro of nitrite from sodium nitroprusside (IC50: 200 microM, 500 microM and 100 microM, respectively). Sulphasalazine (31.1 +/- 5% decrease in signal at 1 mM) was less effective than 5-ASA, but sulphapyridine, N-acetyl 5-ASA, indomethacin and hydrocortisone produced no decrease in nitric oxide signal at all.


CONCLUSIONS
Nitric oxide binding may be part of the mechanism by which ASA derivatives exert their therapeutic effect, and this work suggests that it may be an important factor in the pathogenesis of ulcerative colitis.
Reynolds
P D
PD
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, UK.
Middleton
S J
SJ
Shorthouse
M
M
Hunter
J O
JO
D000636:Aminosalicylic Acids / Q000378:metabolism / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005765:Gastrointestinal Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011048:Polarography; D013427:Sulfapyridine / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology
D000636:Aminosalicylic Acids; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D009569:Nitric Oxide; D012460:Sulfasalazine; D013427:Sulfapyridine