Hepatobiliary excretion of bacterial formyl-methionyl peptides in rat
ISSN: |
1573-2568
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Keywords: |
N-formylmethionine leucyl-phenylalanine ; enterohepatic circulation ; bile ; peptides ; inflammatory bowel disease
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Source: |
Springer Online Journal Archives 1860-2000
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Topics: |
Medicine
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Notes: |
Abstract The bacterial chemotactic peptide formyl-met-leu-phe and its radioiodinated analog formyl-met-leu-[125I]tyr are rapidly excreted by the liver into bile following portal or systemic venous infusions in rats or after absorption from the gut lumen. To determine the molecular structural requirements for hepatobiliary excretion of formyl-methionyl peptides, structure-activity studies using portal venous infusions of 24 structural analogs of formyl-met-leu-tyr were performed in rats with biliary cannulae. Hepatic extraction of peptides was studiedin vivo using external gamma counting after portal infusion. Efficient hepatobiliary excretion was not restricted to bioactive formyl peptides, but showed a broad specificity for different amino-acylated (formyl, acetyl, propionyl, carbobenzoxy) di- and tripeptides and no requirement for methionine in position one or for a free carboxy terminus. However, nonacylated peptides and an acyl-amino acid showed little excretion. Hepatic extraction of peptide was also related toN-acylation. Hepatic extraction and excretion ofN-acyl peptides were also related to hydrophobicity. Thus, the presence of anN-acyl group is the key determinant of biliary excretion of inflammatory bacterial f-met peptides in the rat.
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Type of Medium: |
Electronic Resource
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URL: |