beta-Adrenergic stimulation promotes homocysteic acid release from astrocyte cultures: evidence for a role of astrocytes in the modulation of synaptic transmission.

The sulfur-containing amino acid homocysteic acid (HCA) is present in and released from nervous tissue, exerting excitatory effects on neurons by predominantly activating NMDA receptors. It is interesting that HCA appears to be exclusively localized in glial cells, not in neurons. This profile of glial localization and excitatory action on neurons has led to the hypothesis that HCA could participate in intercellular communication in the brain as a "gliotransmitter." To test this hypothesis further, we searched for specific, receptor-mediated stimuli that could induce release of HCA from cultured astrocytes. For this reason we tested the effect of noradrenaline and vasoactive intestinal peptide, two transmitters known to interact with specific receptors on astrocytes, on the release of HCA from these cells. Noradrenaline and the beta-adrenergic agonist isoproterenol induced an efflux of HCA from astrocyte cultures. Further stressing the beta-adrenergic mediation of this effect is the blockade by atenolol of the HCA release evoked by isoproterenol. The stimulation of HCA release from astrocytes was not observed with the alpha-noradrenergic agonist methoxamine and with vasoactive intestinal peptide. These results taken together further strengthen the role of HCA as a gliotransmitter. Its efflux from glia could be controlled by noradrenaline, activating beta-adrenergic receptors on astrocytes. The present study provides the first evidence for an influence of beta-adrenergic receptor activation on the release of an excitatory amino acid from astrocytes and further supports the notion that glial-neuronal interactions play a role in synaptic transmission.