Endothelin Stimulates Phospholipase D in Striatal Astrocytes |
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Authors: | Solange Desagher Jocelyne Cordier Jacques Glowinski Martine Tencé |
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Institution: | Chaire de Neuropharmacologie, INSERM U114, Collège de France, Paris, France |
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Abstract: | Abstract: In primary cultures of mouse striatal astrocytes prelabeled with 3H]myristic acid, endothelin (ET)-1 induced a time-dependent formation of 3H]phosphatidic acid and 3H]diacylglycerol. In the presence of ethanol, a production of 3H]phosphatidylethanol was observed, indicating the activation of a phospholipase D (PLD). ET-1 and ET-3 were equipotent in stimulating PLD activity (EC50 = 2–5 n M ). Pretreatment of the cells with pertussis toxin partially abolished the effect of ET-1, indicating the involvement of a Gi/Go protein. Inhibition of protein kinase C by Ro 31-8220 or down-regulation of the kinase by a long-time treatment with phorbol 12-myristate 13-acetate (PMA) totally abolished the ET-1-induced stimulation of PLD. In contrast, a cyclic AMP-dependent process is not involved in the activation of PLD, because the ET-1-evoked formation of 3H]phosphatidylethanol was not affected when cells were coincubated with either isoproterenol, 8-bromo-cyclic AMP, or forskolin. Acute treatment with PMA also stimulated PLD through a protein kinase C-dependent process. However, the ET-1 and PMA responses were additive. Furthermore, the ET-1-evoked response, contrary to that of PMA, totally depended on the presence of extracellular calcium. These results suggest that at least two distinct mechanisms are involved in the control of PLD activity in striatal astrocytes. Finally, ET-1, ET-3, and PMA also stimulated PLD in astrocytes from the mesencephalon, the cerebral cortex, and the hippocampus. |
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Keywords: | Endothelin Phospholipase D Phospholipase C Protein kinase C Phosphatidic acid Striatal astrocytes |
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