Action of dopamine and dopaminomimetics on synaptosomal Na, K-ATPase in the corpus striatum

Inhibitors of Na+/H+ and Na+/Ca2+ exchange potentiate methamphetamine‐induced dopamine neurotoxicity: possible role of ionic dysregulation in methamphetamine neurotoxicity

“…(1984); Tolkovsky and Richards (1987); Koch and Barish (1994); Orlowski and Grinstein (1997); E Stephans and Yamamoto (1994, 1995); Ferreira et al (1996); Pellegrini‐Giampietro et al (1997); Carriedo et al (1998); Sanchez‐Gomez and Matute (1999); F Chan et al . (1994); G Jeffrey and Gibbs (1976); Rangaraj and Kalant (1978); Angel et al (1985); Komissarov et al . (1985); Shulman and Fox (1996); Nishi et al .…”

“…1994). However, in the setting of METH neurotoxicity, wherein high levels of METH are maintained for an extended time period (either by giving a single high dose or multiple lower doses), Na + /K + ATPase function is likely to be impaired because of either direct (Jeffrey and Gibbs 1976; Rangaraj and Kalant 1978) or indirect (Komissarov et al . 1985; Shulman and Fox 1996; Nishi et al .…”

“…Prolonged Na 1 entry, secondary to protracted DAT activation, would decrease the Na 1 gradient, were it not for the action of neuronal Na 1 / K 1 ATPase, which transports Na 1 out of the DA cell, against a concentration gradient using neuronal ATP (Stahl 1986;Erecinska and Dagani 1990;Erecinska et al 1994). However, in the setting of METH neurotoxicity, wherein high levels of METH are maintained for an extended time period (either by giving a single high dose or multiple lower doses), Na 1 /K 1 ATPase function is likely to be impaired because of either direct (Jeffrey and Gibbs 1976;Rangaraj and Kalant 1978) or indirect (Komissarov et al 1985;Shulman and Fox 1996;Nishi et al 1999) inhibitory effects of METH on the enzyme, and reduced energy stores (ATP) secondary continued Na 1 /K 1 ATPase function (Stahl 1986;Erecinska and Dagani 1990;Erecinska et al 1994). As Na 1 /K 1 ATPase function declines, less Na 1 would be transported out of the cell, resulting in compromise of the Na 1 gradient.…”

“…1997). Second, there is evidence that the function of neuronal Na + /K + ATPase, which plays an essential role in maintaining the Na + gradient, is influenced by amphetamines directly (Jeffrey and Gibbs 1976; Rangaraj and Kalant 1978) or indirectly (Komissarov et al . 1985; Shulman and Fox 1996; Nishi et al .…”

“…In particular, with each molecule of substrate transported by the DAT, at least two Na 1 ions are co-transported into the DA terminal (Krueger 1990;Gu et al 1994;Sonders et al 1997). Second, there is evidence that the function of neuronal Na 1 /K 1 ATPase, which plays an essential role in maintaining the Na 1 gradient, is in¯uenced by amphetamines directly (Jeffrey and Gibbs 1976;Rangaraj and Kalant 1978) or indirectly (Komissarov et al 1985;Shulman and Fox 1996;Nishi et al 1999), such that after initial period of stimulated enzyme activity, there is phase of decreased enzyme activity. Acting in concert, these two effects of METH (prolonged DAT activation and subsequent Na 1 /K 1 ATPase inhibition) could gradually compromise the Na 1 gradient, and thereby impair the function of Na 1 /H 1 and/or Na 1 /Ca 21 exchangers, since these exchangers use the driving force of the Na 1 gradient to expel excess H 1 and Ca 21 ions out of cells (Kaczorowski et al 1984;Tolkovsky and Richards 1987;Koch and Barish 1994;Orlowski and Grinstein 1997).…”