In vitro effects of l-arginine and guanidino compounds on NTPDase1 and 5′-nucleotidase activities from rat brain synaptosomes

Abstract

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 25μM. Besides this, NA and AA activated ATP hydrolysis at a lower concentration (1μM). 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.