title: Enterohepatic circulation of bacterial chemotactic peptide in rats with experimental colitis.
abstract: The association of hepatobiliary disorders with colonic inflammation is well recognized. Although the pathophysiology is obscure, increased permeation of toxic bacterial products across the inflamed gut to the portal circulation might be one mechanism. Potentially toxic metabolites include N-formylated chemotactic peptides that are produced by several species of intestinal bacteria and can be detected in colonic fluid in vivo. To investigate the metabolic fate of one of these low molecular weight proinflammatory peptides, N-formyl L-methionine L-leucine 125I-L-tyrosine was introduced into colon loops of healthy rats (n = 10) and rats with experimental colitis (n = 15) induced by rectal instillation of 15% (vol/vol) acetic acid. Gut, liver, and blood radioactivity were monitored by external gamma-counting and radioactivity in bile was measured by biliary catheter drainage into a well counter. Bile was processed by high-performance liquid chromatography to determine the amount of intact, bioactive peptide excreted over 3 h. After colonic instillation of 1 nmol of peptide, the mean (+/- SEM) biliary excretion of intact peptide was 6.4 +/- 2.0 pmol in normal rats and 49.0 +/- 20 pmol in rats with colitis (p less than 0.01). An enterohepatic circulation of synthetic N-formyl L-methionine L-leucine L-tyrosine has been demonstrated in the rat. Experimental colitis was associated with an eightfold increase in biliary excretion of this proinflammatory bacterial peptide. Proinflammatory bacterial peptides synthesized by colonic bacteria could be important in the pathophysiology of colon inflammation and its frequently associated hepatobiliary complications.
authors.affiliation: Wellcome Medical Research Institute, Dunedin, New Zealand.
authors.forename: C H
authors.initials: CH
authors.lastname: Hobson
authors.forename: T J
authors.initials: TJ
authors.lastname: Butt
authors.forename: D M
authors.initials: DM
authors.lastname: Ferry
authors.forename: J
authors.initials: J
authors.lastname: Hunter
authors.forename: V S
authors.initials: VS
authors.lastname: Chadwick
authors.forename: M F
authors.initials: MF
authors.lastname: Broom
mesh_terms: D000085:Acetates / Q000633:toxicity; D019342:Acetic Acid; D000818:Animals; D002630:Chemotactic Factors / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000473:pathology; D004764:Enterohepatic Circulation; D007457:Iodine Radioisotopes; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000085:Acetates; D002630:Chemotactic Factors; D007457:Iodine Radioisotopes; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042203:N-formylmethionyl-leucyl-tyrosine; D019342:Acetic Acid