MODIFICATION OF STRIATAL ARGININE AND CITRULLINE METABOLISM BY NITRIC-OXIDE SYNTHASE INHIBITORS

THE effects of N-G-substituted L-arginine (ARG) analogues on striatal ARG and citrulline (CIT) levels were investigated using in vivo microdialysis technique. A microdialysis probe was implanted into the striatum of anaesthetized Sprague-Dawley rats. Direct intrastriatal perfusion with 1 mM N-G-nitro-L-arginine methyl ester (n = 8) increased striatal ARG release and decreased CIT release, suggesting suppressed NO synthase activity in the tissue. On the other hand, 1 mM N-G-monomethyl-L-arginine (L-NMMA) (n = 6) evoked a persistent increase in both ARG and CIT. Considering that 4-320 mu M L-ARG (n = 8) failed to increase CIT formation, CIT seems to be synthesized in the striatal tissue from L-NMMA by the enzyme that has been demonstrated in the kidney and aortic endothelium (N-G,N-G-dimethylarginine dimethylaminohydrolase).