Muscella A, Aloisi F, Marsigliante S, Levi G
Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
J Neurochem. 2000 Mar;74(3):1325-31. doi: 10.1046/j.1471-4159.2000.741325.x.
In astrocytes the activity of the Na+,K(+)-ATPase pump maintains an inwardly directed electrochemical sodium gradient used by the Na+-dependent transporters and regulates the extracellular K+ concentration essential for neuronal excitability. We show here that incubation of cultured rat astrocytes with angiotensin II (Ang II) modulates Na+,K(+)-ATPase activity, in a dose- and time-dependent manner. Na+,K(+)-ATPase activation was mediated by binding of Ang II to AT1 receptors as it was completely blocked by DuP 753, a specific AT1 receptor subtype antagonist. Stimulation of Na+,K(+)-ATPase activity by Ang II was dependent on protein kinase C (PKC) activation because PKC antagonists abolished the inducing effect of Ang II and the PKC activator phorbol 12-myristate 13-acetate enhanced transporter activity. Ang II stimulated translocation of PKC-delta but not that of other PKC isoforms from the cytosol to the plasma membrane. These results indicate that the activity of Na+,K(+)-ATPase in astrocytes is increased by physiological concentrations of Ang II and that the AT1 receptor subtype mediates the Na+,K(+)-ATPase response to Ang II via PKC-delta activation.
在星形胶质细胞中，Na⁺,K⁺-ATP酶泵的活性维持着一种内向的电化学钠梯度，该梯度被钠依赖性转运体所利用，并调节对神经元兴奋性至关重要的细胞外钾离子浓度。我们在此表明，用血管紧张素II（Ang II）孵育培养的大鼠星形胶质细胞，会以剂量和时间依赖性方式调节Na⁺,K⁺-ATP酶的活性。Na⁺,K⁺-ATP酶的激活是由Ang II与AT1受体结合介导的，因为它被特异性AT1受体亚型拮抗剂DuP 753完全阻断。Ang II对Na⁺,K⁺-ATP酶活性的刺激依赖于蛋白激酶C（PKC）的激活，因为PKC拮抗剂消除了Ang II的诱导作用，而PKC激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯增强了转运体活性。Ang II刺激PKC-δ从细胞质向质膜的转位，但不刺激其他PKC同工型的转位。这些结果表明，生理浓度的Ang II会增加星形胶质细胞中Na⁺,K⁺-ATP酶的活性，并且AT1受体亚型通过PKC-δ激活介导Na⁺,K⁺-ATP酶对Ang II的反应。
