Kyotorphin (L-tyrosyl-L-arginine) as a possible substrate for inducible nitric oxide synthase in rat glial cells.
L-Arginine (L-Arg) is an endogenous substrate for nitric oxide synthase (NOS). In the present study, we examined whether L-tyrosyl-L-Arg (kyotorphin), an endogenous analgesic neuropeptide, might be a substrate for inducible NOS (iNOS) in the brain. Both kyotorphin and L-Arg caused an accumulation of nitrites in lipopolysaccharide (LPS)-treated glial cells cultured from infant rat brains. However, such accumulation of nitrites was not induced by NG-nitro-L-Arg (a NOS inhibitor), L-tyrosyl-D-Arg (D-kyotorphin) or D-Arg. L-Leucyl-L-Arg (an antagonist for kyotorphin receptors) or bestatin (an inhibitor for kyotorphin-hydrolyzing peptidase) did not inhibit the kyotorphin-induced accumulation of nitrites in LPS-treated cells. On the contrary, L-Leucyl-L-Arg caused an accumulation of nitrites in a concentration-dependent manner. The results indicate that nitric oxide (NO) is produced in LPS-treated glial cells directly from kyotorphin through the catalytic action of iNOS.
Arima
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Kitamura
Y
Y
Nishiya
T
T
Takagi
H
H
Nomura
Y
Y
D000700:Analgesics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004723:Endorphins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides; D009457:Neuroglia / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
D000700:Analgesics; D004151:Dipeptides; D004723:Endorphins; D008070:Lipopolysaccharides; C019448:kyotorphin; C078789:leucylarginine; D014443:Tyrosine; D001120:Arginine; D019001:Nitric Oxide Synthase