title: Costimulation of N-methyl-D-aspartate and muscarinic neuronal receptors modulates gap junctional communication in striatal astrocytes.
abstract: Cocultures of neurons and astrocytes from the rat striatum were used to determine whether the stimulation of neuronal receptors could affect the level of intercellular communication mediated by gap junctions in astrocytes. The costimulation of N-methyl-D-asparte (NMDA) and muscarinic receptors led to a prominent reduction of astrocyte gap junctional communication (GJC) in coculture. This treatment was not effective in astrocyte cultures, these cells being devoid of NMDA receptors. Both types of receptors contribute synergistically to this inhibitory response, as the reduction in astrocyte GJC was not observed after the blockade of either NMDA or muscarinic receptors. The involvement of a neuronal release of arachidonic acid (AA) in this inhibition was investigated because the costimulation of neuronal NMDA and muscarinic receptors markedly enhanced the release of AA in neuronal cultures and in cocultures. In addition, both the reduction of astrocyte GJC and the release of AA evoked by NMDA and muscarinic receptor costimulation were prevented by mepacrine, a phospholipase A(2) inhibitor, and this astrocyte GJC inhibition was mimicked by the exogenous application of AA. Metabolites of AA formed through the cyclooxygenase pathway seem to be responsible for the effects induced by either the costimulation of NMDA and muscarinic neuronal receptors or the application of exogenous AA because, in both cases, astrocyte GJC inhibition was prevented by indomethacin. Altogether, these data provide evidence for a neuronal control of astrocytic communication and open perspectives for the understanding of the modalities through which cholinergic interneurons and glutamatergic inputs affect local circuits in the striatum.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U114, Collège de France, 11, Place Marcelin Berthelot, 75005 Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Rouach
authors.forename: M
authors.initials: M
authors.lastname: Tencé
authors.forename: J
authors.initials: J
authors.lastname: Glowinski
authors.forename: C
authors.initials: C
authors.lastname: Giaume
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
chemical_list: D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D016718:Arachidonic Acid; D016202:N-Methylaspartate; D002217:Carbachol; D000109:Acetylcholine