Inhibition of Na+, K+-ATPase activity in rat striatum by guanidinoacetate.
The aim of this work was to investigate the effect of guanidinoacetate (GAA), the principal metabolite accumulating in guanidinoacetate methyltransferase (GAMT)-deficiency, on Na(+), K(+)-ATPase, Mg(2+)-ATPase and acetylcholinesterase (AChE) activities in striatum of young rats. We also studied the kinetics of the inhibition of Na(+), K(+)-ATPase activity caused by guanidinoacetate. Guanidinoacetate did not alter acetylcholinesterase and Mg(2+)-ATPase activities, but significantly inhibited Na(+), K(+)-ATPase activity. The apparent K(m) and V(max) of Na(+), K(+)-ATPase for ATP as substrate were 0.20mM and 0.82nmol inorganic phosphate (Pi) released per min per mg of protein, respectively. K(i) value was 7.18mM, and the inhibition was of the uncompetitive type. The results also showed a competition between guanidinoacetate and argininic acid (AA), suggesting a common binding site for the guanidino compounds (GC) on the enzyme. It is proposed that Na(+), K(+)-ATPase inhibition by guanidinoacetate may be one of the mechanisms involved in the neuronal dysfunction observed in GAMT-deficiency and in other diseases which accumulate guanidinoacetate.
Zugno
Alexandra I
AI
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.
Stefanello
Francieli M
FM
Streck
Emilio L
EL
Calcagnotto
Thiago
T
Wannmacher
Clóvis M D
CM
Wajner
Moacir
M
Wyse
Angela T S
AT
D000110:Acetylcholinesterase / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D050937:Guanidinoacetate N-Methyltransferase; D066298:In Vitro Techniques; D007700:Kinetics; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000201:enzymology
C000225:argininic acid; D001120:Arginine; C494508:Gamt protein, rat; D050937:Guanidinoacetate N-Methyltransferase; D000110:Acetylcholinesterase; D000254:Sodium-Potassium-Exchanging ATPase; C004946:glycocyamine; D005998:Glycine