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Transport of l ‐[ 3 H]Arginine in Cultured Neurons: Characteristics and Inhibition by Nitric Oxide Synthase Inhibitors
Author(s) -
Westergaard Niels,
Beart Philip M.,
Schousboe Arne
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03579.x
Subject(s) - nitric oxide , arginine , nitric oxide synthase , neocortex , biochemistry , chemistry , amino acid , intracellular , biology , biophysics , neuroscience , organic chemistry
To investigate whether transport of l ‐arginine into neurons plays an integral role in the metabolism of the novel neuromodulator nitric oxide, the uptake of l ‐[ 3 H]arginine was characterized in cultured neurons of mouse cerebellum and cerebral cortex (neocortex). The transport of l ‐[ 3 H]arginine was saturable and monophasic into both types of neurons with an apparent K m of 100 μM and V max of 2.6 nmol/min/mg of protein. The transport process was stereospecific, and the pattern of inhibition by basic l ‐amino acids was consistent with a “y + ” transport system. The potencies with regard to inhibition of l ‐arginine uptake of the two inhibitors of nitric oxide synthase, N G ‐monomethyl‐ l ‐arginine and N G ‐amino‐ l ‐arginine (IC 50 values of 120 and 65 μM , respectively), suggest that these nitric oxide synthase inhibitors may also reduce formation of nitric oxide and cyclic GMP via a block of arginine uptake. Overall, these data indicate that uptake of l ‐arginine could regulate its intracellular concentration and, consequently, its availability for synthesis of nitric oxide.