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 synthas e (NOS). In the present study, we examined whether L-tyrosyl-L-Arg (ky otorphin), an endogenous analgesic neuropeptide, might be a substrate for inducible NOS (iNOS) in the brain. Both kyotorphin and L-Arg cause d an accumulation of nitrites in lipopolysaccharide (LPS)-treated glia l cells cultured from infant rat brains. However, such accumulation of nitrites was not induced by N-G-nitro-L-Arg (a NOS inhibitor), L-tyro syl-D-Arg (D-kyotorphin) or D-Arg. L-Leucyl-L-Arg (an antagonist for k yotorphin receptors) or bestatin (an inhibitor for kyotorphin-hydrolyz ing 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 r esults indicate that nitric oxide (NO) is produced in LPS-treated glia l cells directly from kyotorphin through the catalytic action of iNOS.