CHEMOTACTIC PEPTIDE EFFECTS ON INTESTINAL ELECTROLYTE TRANSPORT

The bacterial-derived chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) increases short-circuit current (I(sc)) and arachidonic acid metabolism (AAM) in rabbit ileum and distal colon. Serosal (s) or mucosal (m) addition of fMLP transiently increases I(sc). Half-maximally effective dose and maximal increases in I(sc) were 32 nM and 84-mu-A/cm2 in ileum and 234 nM and 80-mu-A/cm2 in colon, respectively. Piroxicam, a cyclooxygenase inhibitor, diminished the I(sc) response by 97% in colon and 69% in ileum. Changes in I(sec) were dependent on Cl- and HCO-3 in the bathing media. In ileum, fMLP inhibited m-to-s Cl-36- fluxes and stimulated s-to-m Cl-36- fluxes. These changes in Cl- flux were also inhibited by piroxicam. fMLP stimulated prostaglandin E2 (PGE2) release in intact tissue and in isolated subepithelial components. Increased tissue adenosine 3',5'-cyclic monophosphate levels were detected in intact tissue but not in isolated components. Previous desensitization of ileum to PGE1 inhibited fMLP stimulation of I(sc) in ileum by 88%. Desensitization to fMLP in ileum failed to alter the effect of PGE1 (10-mu-M) on I(sc). In isolated microsomal membranes of ileal enterocytes, fMLP binding sites could not be demonstrated, suggesting that fMLPs action was initially mediated via stimulation of nonepithelial cell cyclooxygenase activity. The above results indicate that fMLP stimulates net secretion in both ileum and colon probably by the activation of AAM.