Catecholamine과 금속이온의 킬레이트제가 synaprosome의 Na^+-K^+ ATPase의 활성도에 미치는 영향 = Effects of Catecholamines and Metal Chelators on Synaptosomal Na^+-K^+ ATPase Activity

다국어 초록 (Multilingual Abstract)

The Na^+-K^+ ATPase activity of the synaptic membranes appears to have an important role in the regulation of neurotransmitter release and uptake. Although it is well known that
stimulate the activity of neuronal membrane Na^+-K^+ ATPase, the mechanism by which catecholamines increase Na^+-K^+ ATPase activity is unclear. It is suggested that there is a direct linkage between adrenoceptors and Na^+-K^+ ATPase. While, some investigators reported that norepinephrine increased the activity of neurally derived Na^+-K^+ ATPase through elimination of inhibitory influence of metal ions by forming metal-norepinephrine complex.
In the present study, therefore,a linkage between adrenoceptors and Na^+-K^+ ATPase or Mg^++ ATPase was studied by investigating effects of catecholamines on synaptosomal Na^+-K^+ ATPase and Mg^++ ATPase with or without antagonists for adrenoceptors. Effects of various chelating agents on Na^+-K^+ ATPase and Mg^++ ATPase activities in the presence and absence of metal ions were also examined. In addition, inhidition of ATPase by metal ions which may be associated with lipid peroxidation and action of oxygen radicals produced was investigated.
Na^+-K^+ ATPase and Mg^++ ATPase activities in brain cortex synaptosomes of rat were increased by both norepinephrine and dopamine in a dose dependent manner. The effects of catecholamines on these ATPase were antagonized by yohimbine, phentolamine and propranolol. Metal ion chelators such as EDTA, DETAPAC, penicillamine and EGTA clearly increased Na^+-K^+ ATPase and Mg^++ ATPase activities with or without metal ions. Activation of these ATPases was further stimulated by catecholamines but was not affected by antagonists. When synaptosomes were incubated with Fe^++ or Cu^++, both production of malondialdehyde from synaptosomes and inactivation of ATPases were observed and these phenomena were prevented by catecholamines, DETAPAC, penicillamine, superoxide dismutase which is a scavenger of O_2 and catalase which is a scavenger of H_2O_2.
The results obtained suggest that there is a linkage between α-or β-adrenoceptors and Na^+-K^+ ATPase and Mg^++ ATPase through their action on adrenoceptors. Chelating agents of metal ions showed a stimulatory effect on synaptosomal Na^+-K^+ ATPase and Mg^++ ATPase through their action on adrenoceptors. Chelating agents of metal ions showed a stimulatory effect on synaptosomal Na^+-K^+ ATPase and Mg^++ ATPase by reversal of metal inhibition of these ATPases. Catecholamines may mimic the effects of chelating agents of metal ions and regulate synaptosomal Na^+-K^+ ATPase by reliving inactivation of these ATPases or lipid peroxidation cacused by metal ions, particularly Fe^++ and Cu^++.