that has attracted attention as a model bacterial chemotactic A neutrophil chemotactic factor N-formyl-methionylfactor. Studies in healthy rats have shown that normal intesleucyl-phenylalanine (fMLP), produced by Escherichia tinal mucosa is almost impermeable to fMLP; however, when coli under conditions of intestinal inflammation, is reintestinal inflammation impairs this mucosal barrier, fMLP ported to circulate enterohepatically in the presence of might gain access to the portal or systemic circulation. 4 experimental colitis, but its effect on bile secretion is Hunter et al. 5 report that hepatic extraction of small pepunclear. Therefore, we investigated the effect of fMLP tides (e.g., 2-10 amino acid residues) is determined mainly on bile secretion in a single-pass isolated perfused rat by the hydrophobicity and amino acid sequence. Because liver system. Infusion of fMLP at different concentrafMLP is a hydrophobic tripeptide, this finding is consistent tions (2 mmol/L, 10 mmol/L, and 20 mmol/L) into the portal with the fact that its major excretory pathway is via the bile. vein resulted in excretion into bile in the native form,Enterohepatic circulation of formylpeptide was demonstrated independent of sodium taurocholate (1 mmol/min) infuwhen it was introduced into rat colon, increasing eightfold sion. Excretion of fMLP increased dose dependently, and in magnitude in the presence of experimental colitis induced approximately 12% of the infused dose was detected at by acetic acid 6 and up to 70-fold when intestinal mucosal each concentration. With constant infusion of sodium permeability was enhanced by dithiothreitol. 7 These observataurocholate (1 mmol/min), fMLP (20 mmol/L) increased tions might be relevant to the association between inflammabile flow but decreased phospholipid and cholesterol setory bowel diseases and hepatobiliary disorders such as pericretion. Bile acid secretion was not affected. Phosphocholangitis and sclerosing cholangitis. 8,9 lipid/bile acid molar ratios decreased from 0.069 { 0.002Intestinal permeation of fMLP recently has been studied to 0.038 { 0.002, and cholesterol/bile acid molar ratios extensively 10,11 ; extraction from the portal blood and secretion decreased from 0.0074 { 0.0009 to 0.0029 { 0.0008. Thus, into bile have been demonstrated. However, the effect of administration of fMLP resulted in the uncoupling of fMLP on bile secretion is unclear. The aim of this study was biliary excretion of phospholipid and cholesterol from to characterize the effects of fMLP on bile flow and biliary that of bile acids; this effect proved reversible. The insecretion of bile acids, lipids, and horseradish peroxidase crease in bile flow caused by fMLP infusion appeared to (HRP), a fluid-phase marker of the transcytotic vesicle transresult from osmotic choleresis. When 25 mg of horseradport pathway in the isolated perfused rat liver. We also studish peroxidase, a conventional marker of transcytotic ied associative relationships between fMLP and various bilivesicle transport pathway, was i...