Reynolds P D, Middleton S J, Shorthouse M, Hunter J O
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, UK.
Aliment Pharmacol Ther. 1995 Oct;9(5):491-5. doi: 10.1111/j.1365-2036.1995.tb00411.x.
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.
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.
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.
通过使用灵敏且特异的极谱仪,确定氨基水杨酸衍生物对无细胞体系中一氧化氮生成浓度的影响。
氨基水杨酸衍生物3 - ASA(半数抑制浓度为100微摩尔)、4 - ASA(半数抑制浓度为350微摩尔)和5 - ASA(半数抑制浓度为5微摩尔)均降低了一氧化氮信号。这些药物对硝普钠体外生成亚硝酸盐具有相似的抑制作用(半数抑制浓度分别为200微摩尔、500微摩尔和100微摩尔)。柳氮磺胺吡啶(1毫摩尔时信号降低31.1±5%)的效果不如5 - ASA,但磺胺吡啶、N - 乙酰5 - ASA、吲哚美辛和氢化可的松对一氧化氮信号根本没有降低作用。
一氧化氮结合可能是ASA衍生物发挥治疗作用机制的一部分,并且这项研究表明它可能是溃疡性结肠炎发病机制中的一个重要因素。