Enhanced thromboxane A2 and prostacyclin production by cultured rectal mucosa in ulcerative colitis and its inhibition by steroids and sulfasalazine.
Accumulation of 6-ketoprostaglandin F1 alpha and thromboxane B2, the stable metabolites of prostacyclin I2 and thromboxane A2 respectively, by cultured rectal mucosa obtained from patients with active ulcerative colitis was significantly higher than their respective accumulation by cultured biopsy specimens obtained from normal subjects. Accumulation of prostacyclin I2 and thromboxane A2 by rectal mucosa obtained from ulcerative colitis patients in remission was not enhanced. Prostacyclin I2, thromboxane A2, and prostaglandin E2 accumulation was significantly inhibited by the addition to the culture medium of 5-aminosalicylic acid, flufenamic acid, aspirin, azathioprine, and methylprednisolone. Sulfapyridine inhibited significantly only prostaglandin E2 and prostacyclin I2 while sulfasalazine inhibited thromboxane A2, prostaglandin E2, and prostacyclin I2 accumulation. Flufenamic acid potentiated the inhibition of prostaglandin E2 accumulation induced by methylprednisolone when administered alone. These results suggest that in addition to the mediation by prostaglandin E2, thromboxane A2 and prostacylin I2 may also be involved in the inflammatory response in ulcerative colitis. Moreover, the therapeutic effects of steroid hormones and sulfasalazine may be partially related to their inhibition of colonic prostaglandin E2, prostacyclin I2, and thromboxane A2 synthesis.
D003093:Colitis, Ulcerative / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D011453:Prostaglandins; D011458:Prostaglandins E; D013256:Steroids; D013931:Thromboxanes; D012460:Sulfasalazine; D013928:Thromboxane A2; D011464:Epoprostenol