Adaptation of pancreatic amino acid transport in rats after treatment with the synthetic protease inhibitor camostat mesilate.
Exocrine pancreatic amino acid transport was studied following oral treatment of rats with the synthetic protease inhibitor camostat mesilate. Camostat (200 mg/kg/day) was administered via an orogastric tube for 10 days, and kinetics of amino acid transport were then examined in the isolated perfused pancreas using a dual-isotope dilution technique. Administration of camostat doubled the rate constant (Vmax/Kt) for L-phenylalanine transport via System L by increasing the Vmax from 12.3 +/- 0.4 (n = 12) to 19.6 +/- 2.2 mumol/min/g (n = 4). Although the Kt (35 +/- 2 mM, n = 4) and Vmax (47.7 +/- 1.6 mumol/min/g) for L-serine transport via System asc increased, the Vmax/Kt ratio decreased from a control value of 1.85 to 1.36. Increases in Kt (5 +/- 2 mM, n = 4) and Vmax (5.18 +/- 1.01 mumol/min/g) for L-lysine transport via System y+ were also detected but Vmax/Kt remained unchanged. In the presence of a low Na+ perfusate, influx of L-serine, L-phenylalanine, and L-lysine were inhibited between 36 and 50%. Treatment with camostat results in an increase in the rate and Na+-dependence of large neutral amino acid transport in the rat exocrine pancreas. Pancreatic growth induced by repeated oral administration of camostat appears to be accompanied by an enhanced uptake of precursor amino acids.
Mann
G E
GE
Biomedical Sciences Division, King's College London, U.K.
Muñoz
M
M
D000284:Administration, Oral; D000596:Amino Acids / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism / Q000493:pharmacokinetics; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D004952:Esters; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D010649:Phenylalanine; D016670:Gabexate