Exaggerated prostaglandin production by colonic smooth muscle in rabbit colitis.
Enhanced production of arachidonic acid metabolites by colonic mucosa has been reported in ulcerative colitis as well as in experimental models of colitis. However, production of these compounds by colonic smooth muscle from colitis subjects has not been described. To evaluate arachidonic acid metabolism in colonic tissue, we studied the production of prostaglandin E2 (PGE2) by mucosa and muscularis propria in two experimental models of acute colitis in which inflammation was virtually confined to the mucosa. Colitis was induced in New Zealand white rabbits by either of two methods, dinitrochlorobenzene (DNCB) sensitization or formalin followed by intravenous soluble immune complexes (F-IC). Arachidonic acid metabolites were identified from in vitro incubations of tissue with [14C] arachidonic acid by thin layer chromatography followed by autoradiography. The major eicosanoid metabolites of colitis mucosa and muscularis were 14C-labeled prostaglandin E2, prostaglandin F2a and 6-keto prostaglandin F1 alpha. PGE2 was quantitated from incubations without labeled arachidonic acid by radio-immunoassay. PGE2, expressed as picograms per milligram protein per 20 min (mean +/- SEM), was increased in F-IC mucosa (1093 +/- 141 vs 645 +/- 189, P less than 0.05) and DNCB mucosa (1354 +/- 487 vs 527 +/- 222, P less than 0.05) compared to normals. PGE2 production by uninflamed colitis muscularis propria was also increased five- to eightfold compared to normals for F-IC muscularis (1594 +/- 329 vs 189 +/- 35, P less than 0.005) and DNCB muscularis (1287 +/- 171 vs 225 +/- 72, P less than 0.005). Thus, the adjacent inflammation in colonic mucosa may induce increased eicosanoid production by the uninflamed smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Kao
H W
HW
Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance 90509.
Zipser
R D
RD
D000208:Acute Disease; D000818:Animals; D001095:Arachidonic Acids / Q000032:analysis / Q000378:metabolism; D003092:Colitis / Q000209:etiology / Q000378:metabolism*; D003106:Colon / Q000032:analysis / Q000378:metabolism; D015232:Dinoprostone; D004195:Disease Models, Animal; D008297:Male; D009130:Muscle, Smooth / Q000032:analysis / Q000378:metabolism*; D011453:Prostaglandins / Q000032:analysis / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000032:analysis; D011817:Rabbits; D011863:Radioimmunoassay
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D015232:Dinoprostone