BETA-ADRENERGIC STIMULATION PROMOTES HOMOCYSTEIC ACID RELEASE FROM ASTROCYTE CULTURES - EVIDENCE FOR A ROLE OF ASTROCYTES IN THE MODULATIONOF SYNAPTIC TRANSMISSION
Kq. Do et al., BETA-ADRENERGIC STIMULATION PROMOTES HOMOCYSTEIC ACID RELEASE FROM ASTROCYTE CULTURES - EVIDENCE FOR A ROLE OF ASTROCYTES IN THE MODULATIONOF SYNAPTIC TRANSMISSION, Journal of neurochemistry, 68(6), 1997, pp. 2386-2394
The sulfur-containing amino acid homocysteic acid (HCA) is present in
and released from nervous tissue, exerting excitatory effects on neuro
ns 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 hypo
thesis further, we searched for specific, receptor-mediated stimuli th
at could induce release of HCA from cultured astrocytes. For this reas
on we tested the effect of noradrenaline and vasoactive intestinal pep
tide, two transmitters known to interact with specific receptors on as
trocytes, on the release of HCA from these cells. Noradrenaline and th
e 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 vas
oactive intestinal peptide. These results taken together further stren
gthen 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 in
fluence of beta-adrenergic receptor activation on the release of an ex
citatory amino acid from astrocytes and further supports the notion th
at glial-neuronal interactions play a role in synaptic transmission.