Glial receptors and their intervention in astrocyto-astrocytic and astrocyto-neuronal interactions.
As shown on cultured astrocytes from the mouse, in the presence of adenosine deaminase, 2-chloroadenosine by acting on A1-adenosine receptors potentiated the activation of phospholipase C induced by the alpha 1-adrenergic agonist, methoxamine. This potentiation required the presence of external calcium and was blocked by pertussis toxin. Moreover, this potentiation resulted from a cascade of events: activation (by calcium and protein kinase C) of a phospholipase A2 coupled to A1-adenosine receptors, release of arachidonic acid, which inhibited the reuptake of glutamate into astrocytes and finally additional activation of phospholipase C by externally accumulated glutamate through metabotropic receptors. The effects of 2-chloroadenosine and methoxamine were respectively mimicked by somatostatin and substance P while endothelins reproduced the combined effects of 2-chloroadenosine and methoxamine. Conditioned media from treated astrocytes enriched in glutamate stimulated phospholipase C in cultured striatal neurones. In addition, glutamate alone was also found to stimulate phospholipase A2 in astrocytes through receptors exhibiting a pharmacological profile distinct from metabotropic receptors coupled to phospholipase C and the glutamate response was potentiated by ATP. Moreover, the neuronal arachidonic acid production evoked by glutamate was potentiated by acetylcholine. Finally, the combined application of 2-chloroadenosine and methoxamine on striatal astrocytes reduced the permeability of gap junctions between astrocytes and this response was mimicked by arachidonic acid. Together, these results emphasized the contribution of astrocytes in the regulation of glutamatergic transmission.
Glowinski
J
J
INSERM U.114, Collège de France, Paris.
Marin
P
P
Tence
M
M
Stella
N
N
Giaume
C
C
Premont
J
J
D015762:2-Chloroadenosine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology; D001253:Astrocytes / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D002450:Cell Communication; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology*; D007295:Inositol Phosphates / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D051379:Mice; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000502:physiology
D015220:Calcium Channels; D007295:Inositol Phosphates; D009419:Nerve Tissue Proteins; D011942:Receptors, Adrenergic, alpha; D011956:Receptors, Cell Surface; D015762:2-Chloroadenosine; D016718:Arachidonic Acid; D018698:Glutamic Acid; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D008729:Methoxamine; D002118:Calcium