Glutamate-induced homocysteic acid release from astrocytes: possible implication in glia-neuron signaling.
Glial cells synthesise neuroactive substances and release them upon neurotransmitter receptor activation. Homocysteic acid (HCA), an endogenous agonist for glutamatergic N-methyl-D-aspartate (NMDA) receptors, is predominantly localised in glial cells. We have previously demonstrated the release of HCA from mouse astrocytes in culture following activation of beta-adrenergic receptors. Moreover, a release of HCA has also been observed in vivo upon physiological stimulation of sensory afferents in the thalamus. Here we report the glutamate-induced release of HCA from astrocytes. The effect of glutamate was mediated by the activation of ionotropic (NMDA and non-NMDA) as well as by metabotropic receptors. In addition, the release of HCA was Ca(2+)- and Na(+)-dependent, and its mechanism involved the activation of the Na+/Ca(2+)-exchanger. Furthermore, we provide evidence for the presence of functional NMDA receptors on astrocytes, which are coupled to an intracellular Ca2+ increase via stimulation of the Na+/Ca(2+)-exchanger. Our data thus favour a participation of glial cells in excitatory neurotransmission and corroborate the role of HCA as a "gliotransmitter."
Centre for Research in Psychiatric Neuroscience, Department of Psychiatry, University of Lausanne, Route de Cery, CH-1008 Prilly-Lausanne, Switzerland.
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D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000378:metabolism*; D051379:Mice; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D013460:Sulfur Isotopes / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D013460:Sulfur Isotopes; C013407:benzamil; D006710:Homocysteine; C007956:homocysteic acid; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000584:Amiloride; D002118:Calcium