TY - JOUR
T1 - Sources of arginine for induced nitric oxide synthesis in the isolated perfused liver
AU - Pastor, C. M.
AU - Morris, S. M.
AU - Billiar, T. R.
PY - 1995
Y1 - 1995
N2 - Hepatocytes can be stimulated to express high levels of inducible nitric oxide synthase (iNOS), which utilizes arginine for nitric oxide (NO) synthesis. Hepatocytes also synthesize and catabolize arginine, an intermediate in the urea cycle, raising the possibility that the urea pathway may provide substrate for hepatic NO synthesis. To identify the sources of arginine for iNOS, we measured the release of NO-/2 + NO4/3 and urea in isolated rat livers perfused in a recirculation model with a Krebs- Henseleit-bicarbonate buffer containing either no added amino acid, arginine, or precursors for urea synthesis. To induce iNOS expression, rats were injected with killed Corynebacterium parvum (C. parvum) or with endotoxin. In livers from C. parvum- and endotoxin-treated rats, we found that 1) an intracellular source of arginine exists that provides substrates to iNOS; 2) additional exogenous arginine increases NO synthesis, demonstrating that endogenous arginine is insufficient for maximal NO synthesis; and 3) an increase in the rate of endogenous arginine synthesis within the urea cycle is inefficient in increasing NO synthesis, demonstrating the independence of the two pathways in the liver.
AB - Hepatocytes can be stimulated to express high levels of inducible nitric oxide synthase (iNOS), which utilizes arginine for nitric oxide (NO) synthesis. Hepatocytes also synthesize and catabolize arginine, an intermediate in the urea cycle, raising the possibility that the urea pathway may provide substrate for hepatic NO synthesis. To identify the sources of arginine for iNOS, we measured the release of NO-/2 + NO4/3 and urea in isolated rat livers perfused in a recirculation model with a Krebs- Henseleit-bicarbonate buffer containing either no added amino acid, arginine, or precursors for urea synthesis. To induce iNOS expression, rats were injected with killed Corynebacterium parvum (C. parvum) or with endotoxin. In livers from C. parvum- and endotoxin-treated rats, we found that 1) an intracellular source of arginine exists that provides substrates to iNOS; 2) additional exogenous arginine increases NO synthesis, demonstrating that endogenous arginine is insufficient for maximal NO synthesis; and 3) an increase in the rate of endogenous arginine synthesis within the urea cycle is inefficient in increasing NO synthesis, demonstrating the independence of the two pathways in the liver.
KW - Corynebacterium parvum
KW - arginase
KW - endotoxin
KW - nitric oxide synthase
KW - urea
UR - http://www.scopus.com/inward/record.url?scp=0029558190&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.1995.269.6.g861
DO - 10.1152/ajpgi.1995.269.6.g861
M3 - Article
C2 - 8572217
AN - SCOPUS:0029558190
SN - 0193-1857
VL - 269
SP - G861-G866
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 6 32-6
ER -