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Inhibition of Na + , K + ‐ATPase activity in rat striatum by the metabolites accumulated in Lesch–Nyhan disease
Author(s) -
Bavaresco Caren S.,
Zugno Alexandra I.,
Tagliari Bárbara,
Wannmacher Clóvis 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.2003.11.002
Subject(s) - striatum , chemistry , atpase , medicine , endocrinology , biochemistry , biology , dopamine , enzyme
In the present study, we investigated the in vitro effect of hypoxanthine, xanthine and uric acid, metabolites accumulating in tissue of patients with Lesch–Nyhan disease, on Na + , K + ‐ATPase activity in striatum of neonate rats. Results showed that all compounds significantly inhibited Na + , K + ‐ATPase activity. We also studied the kinetics of the inhibition of Na + , K + ‐ATPase activity caused by hypoxanthine. The apparent K m and V max of Na + , K + ‐ATPase activity for ATP as the substrate and hypoxanthine as the inhibitor were 0.97 mM and 0.69 nmol inorganic phosphate (Pi) released per min per mg of protein, respectively. K i ‐value was 1.9 μM, and the inhibition was of the non‐competitive type. We also observed that the inhibitory effects of hypoxanthine, xanthine and uric acid probably occur through the same mechanism, suggesting a common binding site for these oxypurines on Na + , K + ‐ATPase. Therefore, it is conceivable that inhibition of brain Na + , K + ‐ATPase activity may be involved at least in part in the neuronal dysfunction characteristic of patients with Lesch–Nyhan disease.