In vitro inhibition of Na+,K+-ATPase activity from rat cerebral cortex by guanidino compounds accumulating in hyperargininemia

Hyperargininemia is a metabolic disorder biochemically characterized by tis sue accumulation of arginine (Arg) and other guanidino compounds (GC). Conv ulsions, lethargy and psychomotor delay are predominant clinical features o f this disease. Considering that some GC are epileptogenic and cause a decr ease in membrane fluidity and that Na+,K+-ATPase, a membrane-bound enzyme, is essential for cellular excitability and is decreased in experimental and human epilepsy, in the present study we determined the in vitro effects of Arg, N-acetylarginine (NAA), argininic acid (AA) and homoarginine (HA) on the activity of Na+,K+-ATPase in the synaptic plasma membrane from cerebral cortex of young rats in the hope to identify a possible mechanism for the brain damage in hyperargininemia. The results showed that all GC tested, ex cept Arg, significantly inhibited Na+,K+-ATPase activity at concentrations similar to those observed in plasma and CSF of patients with hyperargininem ia. In addition, competition between NAA, AA and I-IA for the binding to th e enzyme was observed, suggesting a common binding site for the GC. it is t herefore possible that the inhibitory effect of GC on Na+,Ki-ATPase may be related to the brain dysfunction observed in hyperargininemia. (C) 1999 Els evier Science B.V. All rights reserved.