The pH modulator chloroquine blocks trypsinogen activation peptide generation in cerulein-induced pancreatitis.
OBJECTIVE
We examined the effects of a weak base, chloroquine, on the trypsinogen processing in cerulein-induced pancreatitis.


METHODS
Immunofluorescence studies were performed using newly generated affinity-purified antibodies to the trypsinogen activation peptide (TAP).


RESULTS
The present study showed that chloroquine pretreatment blocked intracellular TAP generation in cerulein-induced pancreatitis.


CONCLUSIONS
These results indicate that intracellular trypsinogen activation, which plays an important role in acute pancreatitis, requires a low-pH compartment, as well as serine protease activity.
Seyama
Yasuji
Y
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
Otani
Taiichi
T
Matsukura
Akira
A
Makuuchi
Masatoshi
M
D000818:Animals; D002108:Ceruletide; D002738:Chloroquine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D009842:Oligopeptides / Q000096:biosynthesis* / Q000276:immunology; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D014362:Trypsinogen / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009842:Oligopeptides; C080396:trypsinogen activation peptide; D002738:Chloroquine; D002108:Ceruletide; D014362:Trypsinogen