Kosenko E, Kaminsky Y, Grau E, Miñana M D, Marcaida G, Grisolía S, Felipo V
Instituto de Investigaciones Citologicas de la Fundación Valenciana de Investigaciones Biomédicas, Valencia, Spain.
J Neurochem. 1994 Dec;63(6):2172-8. doi: 10.1046/j.1471-4159.1994.63062172.x.
Injection of large doses of ammonia into rats leads to depletion of brain ATP. However, the molecular mechanism leading to ATP depletion is not clear. The aim of the present work was to assess whether ammonium-induced depletion of ATP is mediated by activation of the NMDA receptor. It is shown that injection of MK-801, an antagonist of the NMDA receptor, prevented ammonia-induced ATP depletion but did not prevent changes in glutamine, glutamate, glycogen, glucose, and ketone bodies. Ammonia injection increased Na+,K(+)-ATPase activity by 76%. This increase was also prevented by previous injection of MK-801. The molecular mechanism leading to activation of the ATPase was further studied. Na+,K(+)-ATPase activity in samples from ammonia-injected rats was normalized by "in vitro" incubation with phorbol 12-myristate 13-acetate, an activator of protein kinase C. The results obtained suggest that ammonia-induced ATP depletion is mediated by activation of the NMDA receptor, which results in decreased protein kinase C-mediated phosphorylation of Na+,K(+)-ATPase and, therefore, increased activity of the ATPase and increased consumption of ATP.
向大鼠注射大剂量氨会导致脑ATP耗竭。然而，导致ATP耗竭的分子机制尚不清楚。本研究的目的是评估铵诱导的ATP耗竭是否由NMDA受体激活介导。结果表明，注射NMDA受体拮抗剂MK-801可防止氨诱导的ATP耗竭，但不能防止谷氨酰胺、谷氨酸、糖原、葡萄糖和酮体的变化。注射氨使Na +,K(+)-ATP酶活性增加了76%。预先注射MK-801也可防止这种增加。进一步研究了导致ATP酶激活的分子机制。用蛋白激酶C激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯“体外”孵育后，注射氨的大鼠样本中的Na +,K(+)-ATP酶活性恢复正常。所得结果表明，氨诱导的ATP耗竭由NMDA受体激活介导，这导致蛋白激酶C介导的Na +,K(+)-ATP酶磷酸化减少，因此ATP酶活性增加，ATP消耗增加。
