Premium
Evaluation of the mechanism underlying the inhibitory effect of guanidinoacetate on brain Na + , K + ‐ATPase activity
Author(s) -
Zugno Alexandra I.,
Franzon Renata,
Chiarani Fábria,
Bavaresco Caren S.,
Wannmacher Clovis M.D.,
Wajner Moacir,
Wyse Angela T.S.
Publication year - 2004
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2004.05.002
Subject(s) - trolox , taurine , chemistry , nitric oxide , glutathione , arginine , atpase , creatine , biochemistry , inhibitory postsynaptic potential , medicine , enzyme , endocrinology , antioxidant , biology , amino acid , organic chemistry , dpph
Guanidinoacetate methyltransferase deficiency (GAMT‐deficiency) is an inherited neurometabolic disorder clinically characterized by epilepsy and mental retardation and biochemically by accumulation of guanidinoacetate (GAA) and depletion of creatine. Although the neurological symptoms are predominant, the pathogenesis of the brain dysfunction in this disorder is not yet established. In the present study we investigated the in vitro effect of GAA on Na + , K + ‐ATPase and Mg 2+ ‐ATPase activities in synaptic plasma membrane from hippocampus of young rats. Results showed that GAA significantly inhibited Na + , K + ‐ATPase activity without affecting Mg 2+ ‐ATPase activity. We also evaluated the effect of glutathione (GSH), trolox, N ϖ ‐nitro‐ l ‐arginine methyl ester (L‐NAME) and taurine (Tau) on the inhibition elicited by GAA on Na + , K + ‐ATPase activity. GSH, trolox, L‐NAME and Tau per se did not alter Na + , K + ‐ATPase activity. However, L‐NAME and taurine prevented the inhibitory effect of GAA on this enzyme activity. Our findings suggest that the inhibition of Na + , K + ‐ATPase activity caused by GAA is possibly mediated by nitric oxide (NO) formation and/or synaptic membrane alteration. The present data may contribute to the understanding of the neurological dysfunction characteristic of GAMT‐deficient patients.