Amino acids differentially inhibit the L-[3H]arginine transport and nitric oxide synthase in rat brain synaptosomes.
The nitric oxide synthase (NOS) present in the cytosol obtained from rat cerebral cortex synaptosomes was inhibited by NG-nitro-L-arginine (L-NOArg) with an IC50 value of approximately 0.06 microM. This compound did not affect the transport of L-arginine (L-Arg) into synaptosomes at concentrations up to 100 microM but other potential inhibitors of NOS (NG-monomethyl-L-arginine, NG-amino-L-arginine and L-arginine methyl ester) inhibited L-Arg transport at a concentration < 5 microM. We showed that concentrations of L-NOArg (0.001-3 microM) that did not block the uptake of tritiated arginine (L-[3H]Arg) inhibited the catalytic activity of NOS in intact synaptosomes. L-NOArg at a concentration of 1 microM inhibited the cytosolic enzyme by 98.0 +/- 2.0% of the total NOS activity whereas the enzyme studied in the intact synaptosomes was only inhibited by 75 +/- 5% which suggested that the NOS in synaptosomes is not fully accessible to the external L-NOArg. On the other hand, L-Lysine did not inhibit the cytosolic NOS activity of ruptured synaptosomes but at a concentration that blocked 50.0 +/- 4.5% of L-[3H]Arg uptake it inhibited the NOS activity in intact synaptosomes by 12.6 +/- 3.6%, suggesting that the transport of L-Arg may be an important regulatory step in the pathway for nitric oxide generation.[1]References
- Amino acids differentially inhibit the L-[3H]arginine transport and nitric oxide synthase in rat brain synaptosomes. Lopes, M.C., Cardoso, S.A., Schousboe, A., Carvalho, A.P. Neurosci. Lett. (1994) [Pubmed]
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