GABA inhibits endozepine release from cultured rat astrocytes

In the mammalian brain, the endogenous ligands for benzodiazepine receptors (also called endozepines) are predominantly synthesized by glial cells. It ; has recently been reported that rat astrocytes in primary culture release substantial amounts of endozepines. The aim of the present study was to in vestigate the possible involvement of GABA in the control of endozepine rel ease. Exposure of cultured rat astrocytes to GABA (10(-7) to 10(-5) M) indu ced a dose-related inhibition of endozepine secretion. At higher doses (3 x 10(-5) to 10(-3) M), the effect of GABA gradually diminished. The inhibito ry effect of GABA (10(-5) M) was mimicked by the GABAB receptor agonist bac lofen (10(-5) M). In contrast, the GABAA receptor agonists 3APS and isoguva cine (10(-5) M each) did not modify endozepine release. The inhibition of e ndozepine secretion evoked by GABA and baclofen (10(-5) M each) was totally abrogated by the specific GABA(B) receptor antagonist phaclofen (10(-4) M) . GABA and baclofen caused a significant inhibition of forskolin-evoked pro duction of cAMP in astrocytes and this effect was abolished in the presence of phaclofen. In contrast, isoguvacine had no effect on cAMP production. E xposure of astrocytes to dbcAMP induced a time- and dose-dependent stimulat ion of endozepine release. These data indicate that GABA, acting through GA BAB receptors negatively coupled to adenylyl cyclase, inhibits endozepine r elease from cultured rat astrocytes. The secretion of endozepines thus appe ars to be a valuable marker to monitor astrocyte activity. (C) 1999 Wiley-L iss, Inc.