Tissue accumulation of
arginine (Arg), N-acetylarginine (NA),
argininic acid (AA) and
homoarginine (HA) occurs in
hyperargininemia, an inborn error of the
urea cycle. In the present study, we investigated the in vitro effects of Arg, NA, AA and HA on
NTPDase1 and
5'-nucleotidase activities from synaptosomal cerebral cortex of rats. The results showed that Arg enhances
NTPDase1 activity at the high concentrations tested (1.5 and 3.0mM) for both the
ATP and
ADP nucleotides. Activation was also observed with other guanidino compounds tested: NA, AA and HA activated
ATP and
ADP hydrolysis in all experiments at the concentration of 25 microM. Besides this, NA and AA activated
ATP hydrolysis at a lower concentration (1 microM). In another set of experiments, we verified the effect of Arg on purified
apyrase at pH 8.0 and 6.5 and observed an increase in the
enzyme activity at all Arg concentrations tested (0.01-3.0mM). In contrast, Arg and the other guanidino compounds tested did not alter
5'-nucleotidase activity. These results suggest that changes in
nucleotide hydrolysis may be involved in the brain dysfunction caused by
hyperargininemia amongst other potential pathophysiological mechanisms involved in this condition.