GLIAL RECEPTORS AND THEIR INTERVENTION IN ASTROCYTO-ASTROCYTIC AND ASTROCYTO-NEURONAL INTERACTIONS

As shown on cultured astrocytes from the mouse, in the presence of ade nosine deaminase, 2-chloroadenosine by acting on A1-adenosine receptor s potentiated the activation of phospholipase C induced by the alpha 1 -adrenergic agonist, methoxamine. This potentiation required the prese nce of external calcium and was blocked by pertussis toxin. Moreover, this potentiation resulted from a cascade of events: activation (by ca lcium and protein kinase C) of a phospholipase A2 coupled to A1-adenos ine receptors, release of arachidonic acid, which inhibited the reupta ke of glutamate into astrocytes and finally additional activation of p hospholipase C by externally accumulated glutamate through metabotropi c receptors. The effects of 2-chloroadenosine and methoxamine were res pectively mimicked by somatostatin and substance P while endothelins r eproduced the combined effects of 2-chloroadenosine and methoxamine. C onditioned media from treated astrocytes enriched in glutamate stimula ted phospholipase C in cultured striatal neurones. In addition, glutam ate alone was also found to stimulate phospholipase A2 in astrocytes t hrough receptors exhibiting a pharmacological profile distinct from me tabotropic receptors coupled to phospholipase C and the glutamate resp onse was potentiated by ATP. Moreover, the neuronal arachidonic acid p roduction evoked by glutamate was potentiated by acetylcholine. Finall y, the combined application of 2-chloroadenosine and methoxamine on st riatal astrocytes reduced the permeability of gap junctions between as trocytes and this response was mimicked by arachidonic acid. Together, these results emphasized the contribution of astrocytes in the regula tion of glutamatergic transmission. (C) 1994 Wiley-Liss, Inc.