6-cyano-7-nitroquinoxaline-2-3-dione and benzamil

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."

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Amiloride; Animals; Animals, Newborn; Astrocytes; Calcium; Cells, Cultured; Cerebral Cortex; Chromatography, High Pressure Liquid; Drug Interactions; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Glutamic Acid; Homocysteine; Mice; Models, Neurological; Neurons; Sulfur Isotopes