Influence of sulfasalazine, 5-aminosalicylic acid and sulfapyridine on prostanoid synthesis and metabolism in rabbit colonic mucosa

Abstract

The effects of sulfasalazine (SASP) and its cleavage products 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) on prostanoid (PG) synthesis and degradation were determined in rabbit colonic mucosa fractions in vitro. When the microsomal fraction was incubated with (14C) arachidonic acid, 10 −3 M SASP and SP did not markedly change the formation of labeled PGE 2, PGF 2α, TxB 2 and 6-keto-PGF 1α. 10 −4 M 5-ASA increased synthesis synthesis about 2.7-fold; the pattern of PG identified was unaltered. In the presence of the 10-fold higher concentration of 5-ASA, PG synthesis remained elevated at a similar level. When the cytosolic fraction was incubated with (3H)PGE 2, 10 −3 M 5-ASA was without influence and 10 −3 M SP decreased slightly PGE 2 breakdown. However, SASP showed a pronounced inhibitory effect at 10 −5 M and inhibition of PGE 2 degradation was complete at 10 t−3 M SASP. The results are compatible with the assumption that stimulation of PG synthesis by 5-ASA is related to therapeutic benefit in the treatment of ulcerative colitis.