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Portacaval Shunting and Hyperammonemia Stimulate the Uptake of l ‐[ 3 H]Arginine but Not of l ‐[ 3 H]Nitroarginine into Rat Brain Synaptosomes
Author(s) -
Raghavendra Rao V. L.,
Audet R. M.,
Butterworth R. F.
Publication year - 1997
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 - 10.1046/j.1471-4159.1997.68010337.x
Subject(s) - hyperammonemia , medicine , endocrinology , arginine , nitric oxide , chemistry , portacaval shunt , cerebellum , nitric oxide synthase , nitroarginine , stimulation , biochemistry , biology , amino acid , cirrhosis , portal hypertension
Elevated activities of nitric oxide synthase (NOS) have been reported previously in the brains of portacaval‐shunted (PCS) rats, a model of chronic hepatic encephalopathy (HE). As l ‐arginine availability for nitric oxide synthesis depends on a specific uptake mechanism in neurons, we studied the kinetics of l ‐[ 3 H]‐arginine uptake into synaptosomes prepared from the brains of PCS rats. Results demonstrate that l ‐arginine uptake is significantly increased in cerebellum (60%; p < 0.01), cerebral cortex (42%; p < 0.01), hippocampus (56%; p < 0.01), and striatum (51%; p < 0.01) of PCS rats compared with sham‐operated controls. Hyperammonemia in the absence of portacaval shunting also stimulated the transport of l ‐[ 3 H]arginine; kinetic analysis revealed that the elevated uptake was due to increased uptake capacity ( V max ) without any change in affinity ( K m ). Incubation of cerebellar synaptosomes with ammonium acetate for 10 min caused a dose‐dependent stimulation of l ‐[ 3 H]arginine uptake. Neither portacaval shunting nor hyperammonemia had any significant effect on the synaptosomal uptake of N G ‐nitro‐ l ‐[ 3 H]arginine. These studies demonstrate that increased NOS activity observed in experimental HE may result from increased availability of l ‐arginine resulting from a direct stimulatory effect of ammonia on l ‐arginine transport.