Influence of sulfasalazine, 5-aminosalicylic acid and sulfapyridine on prostanoid synthesis and metabolism in rabbit colonic mucosa.
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 PGE2, PGF2 alpha, TxB2 and 6-keto-PGF1 alpha X 10(-4) M 5-ASA increased 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)PGE2, 10(-3) M 5-ASA was without influence and 10(-3) M SP decreased slightly PGE2 breakdown. However, SASP showed a pronounced inhibitory effect at 10(-5) M and inhibition of PGE2 degradation was complete at 10(-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.
Kolassa
N
N
Becker
R
R
Wiener
H
H
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D019804:Mesalamine; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism*; D011817:Rabbits; D013424:Sulfanilamides / Q000494:pharmacology*; D013427:Sulfapyridine / Q000494:pharmacology*; D012460:Sulfasalazine / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D001095:Arachidonic Acids; D011453:Prostaglandins; D013424:Sulfanilamides; D016718:Arachidonic Acid; D012460:Sulfasalazine; D019804:Mesalamine; D005978:Glutathione; D013427:Sulfapyridine