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.

Angiotensin II modulates the activity of Na+/K+ATPase in cultured rat astrocytes via the AT1 receptor and protein kinase C-delta activation

MUSCELLA, Antonella;MARSIGLIANTE, Santo;
2000

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11587/105470
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