Intestinal absorption, metabolism and effects of bacterial chemotactic peptides in rat intestine

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Abstract
N‐formylated chemotactic peptides are produced by intestinal bacteria in vitro and Can be detected in intestinal luminal fluids. The healthy intestine must have mechanisms for preventing absorption of such peptides which can induce an inflammatory response when introduced systemically. Synthetic formyl‐methionyl‐leucyl‐phenylalanine (F‐met‐leu‐3H‐phe) has been used as a model bacterial chemotactic peptide to investigate intestinal absorption and metabolism of such peptides in the rat. Disappearance of tritium‐activity was rapid from jejunal and ileal loops and substantial hydrolysis of peptide occurred with only labelled metabolites appearing in portal blood. Less absorption and less metabolism occurred in the colon. Degradation of F‐met‐leu‐phe was due to a mucosal carboxypeptidase and was inhibited by benzylsuccinate, a potent inhibitor of the enzyme. In the presence of inhibitor, luminal disappearance from ileal loops was abolished and F‐met‐leu‐3H‐phe was not detected in portal blood indicating that healthy gut mucosa is ‘impermeable’ to intact peptide. The intestinal ‘barrier’ preventing mucosal penetration and the inflammatory effects of luminal bacterial peptides have two components: restricted mucosal permeability and a carboxypeptidase capable of hydrolysing such peptides with loss of their bioactivity.