Enterohepatic circulation of bacterial chemotactic peptide in rats with experimental colitis
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 /sup 125/I-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.
- Research Organization:
- Wellcome Medical Research Institute, Dunedin (New Zealand)
- OSTI ID:
- 5201377
- Journal Information:
- Gastroenterology; (United States), Journal Name: Gastroenterology; (United States) Vol. 94:4; ISSN GASTA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BACTERIA
BETA DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DIGESTIVE SYSTEM DISEASES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
GASTROINTESTINAL TRACT
HYDROXY ACIDS
INTERMEDIATE MASS NUCLEI
INTESTINES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LARGE INTESTINE
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLISM
MICROORGANISMS
MOLECULAR WEIGHT
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PEPTIDES
PROTEINS
RADIOISOTOPES
RATS
RODENTS
SEPARATION PROCESSES
TRACER TECHNIQUES
TYROSINE
VERTEBRATES