Somatostatin potentiates the alpha 1-adrenergic activation of phospholipase C in striatal astrocytes through a mechanism involving arachidonic acid and glutamate.
As previously shown with adenosine, somatostatin, which is ineffective alone, enhanced the alpha 1-adrenergic-agonist-stimulated production of inositol phosphates in cultured striatal astrocytes. This effect was suppressed in cells pretreated with pertussis toxin. It required external calcium and was selectively antagonized by both mepacrine, an inhibitor of phospholipase A2, and 5,8,11,14-eicosatetraynoic acid, a nonmetabolizable analog of arachidonic acid. In addition, a long-lasting elevation of cytosolic calcium and a release of arachidonic acid were observed only under the combined stimulation of somatostatin and alpha 1-adrenergic receptors. Arachidonic acid could in turn inhibit glutamate uptake into astrocytes, and the resulting external accumulation of glutamate could account for the somatostatin-evoked amplification of the alpha 1-adrenergic-agonist-stimulated hydrolysis of inositol-phospholipids. The effect of somatostatin was indeed reproduced by glutamate or glutamate uptake inhibitors and suppressed by enzymatic removal of external glutamate. Thus, astrocytes may contribute to long-term plasticity events in glutamatergic synapses through regulation of external glutamate levels.
Laboratoire de Neuropharmacologie, Institut National de la Santé et de la Recherche Médicale U.114, Collège de France, Paris.
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Marin
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Delumeau
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Tence
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Cordier
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Glowinski
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Premont
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism*; D004622:Embryo, Mammalian; D004789:Enzyme Activation; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008729:Methoxamine / Q000494:pharmacology*; D051379:Mice; D008959:Models, Neurological; D037342:Pertussis Toxin; D011796:Quinacrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D005971:Glutamates; D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D013004:Somatostatin; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D011796:Quinacrine; D008729:Methoxamine; D002118:Calcium