Hepatobiliary excretion and enterohepatic circulation of bacterial chemotactic peptide (FMLP) in the rat

Abstract

N-formyl methionyl leucyl 3H-phenylalanine was used as a model bacterial chemotactic peptide to study the systemic metabolism and excretory pathways for such peptides in the rat. After intravenous bolus infusion, the peptide was rapidly cleared from the systemic circulation with a mean of 22% of the dose being excreted in bile over 2 h. In bile, 53% of radioactivity existed as intact peptide, the remainder was its degradation product, 3Hphenylalanine. No intact peptide was detected in urine. While previous studies have shown no significant absorption of F-met-leu-phe from normal rat intestine, in the current studies ileal loop infusions of F-met-leu-phe in hyperosmolar solution, to increase gut permeability, resulted in absorption of intact peptide which was recovered in bile. These studies show that bile is a major pathway for excretion of bacterial chemotactic peptide in the rat and confirm the potential for an enterohepatic circulation of peptides from the gut lumen under conditions of increased intestinal mucosal permeability.

Biliary lactoferrin concentrations are increased in active inflammatory bowel disease: a factor in the pathogenesis of primary sclerosing cholangitis?

“…In the rat, bacterial chemotactic peptides, such as N-formylmethionyl-leucyl-phenylalanine, have been shown to undergo an enterohepatic circulation [8,9] and to induce selective release of neutrophil secondary granule products in vitro [42]. Therefore, in active inflammatory bowel disease, possibly as a result of decreased protease activity within the intestinal lumen [51] and\or increased intestinal mucosal permeability [52,53], biliary concentrations of bacterial oligopeptides may also rise and induce lactoferrin release from neutrophils within the hepatobiliary tract.…”

“…Although the aetiology of PSC is unknown, one hypothesis is that in patients with inflammatory bowel disease, there is an enterohepatic circulation of chemotactic factors (such as N-formyl peptides [8,9]) or of autoantigens [10,11], which may be responsible for the close association of inflammatory bowel disease and PSC.…”

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“…In the rat, bacterial chemotactic peptides, such as N-formylmethionyl-leucyl-phenylalanine, have been shown to undergo an enterohepatic circulation [8,9] and to induce selective release of neutrophil secondary granule products in vitro [42]. In the rat, bacterial chemotactic peptides, such as N-formylmethionyl-leucyl-phenylalanine, have been shown to undergo an enterohepatic circulation [8,9] and to induce selective release of neutrophil secondary granule products in vitro [42].…”

Inflammatory Products of Commensal Bacteria and Gastro-Intestinal Disorders

“…Nevertheless, both in the ileum and colon the mucosal barrier is not 100% efficient and intact peptide ( 1%) was ab sorbed. Absorbed intact peptide was ex creted into bile and underwent the enterohepatic circulation [41], In rats with experi mental colitis, the colonic absorption and enterohepatic circulation of intact peptides increased 8-fold [42] and, when colon loops were pre-treated with dithiothreitol to in crease the mucosal permeability, absorption and biliary recovery increased 50-fold [43]. There was a good correlation between changes in colonic mucosal permeability measured by [5lCr]-EDTA absorption and biliary recovery of F-met peptide [43].…”