Neurotransmitters which increase intracellular cAMP levels can cause c
ultured astroglia to change from a flat, polygonal shape to a stellate
morphology. Little is known about how glial stellation can be regulat
ed by other transmitters. In the present study, we demonstrated that L
-glutamate blocked isoproterenol(ISO) or dibutyryl-cAMP induced stella
tion in astroglia. The glutamate inhibition was concentration dependen
t, with its maximal effect on > 90% of cells at 500 mu M. Glutamate al
so reversed glial stellation within a short period (< 30 min). Glutama
te uptake analogues, D-glutamate and D-aspartate, rather than receptor
agonists, kainate and quisqualate, mimicked the glutamate effect. Lik
ewise, the glutamate uptake blocker, D-thero-beta-hydroxyaspartate, bl
ocked the glutamate effect. The glutamate inhibition was not a result
of inhibition of cAMP formation, since norepinephrine, which inhibited
80% of ISO-stimulated cAMP, also caused glial stellation. Increases i
n extracellular K+ to 50 mM also reduced glial stellation, whereas 25
mM K+ had little effect. Since 25 mM K+ caused much greater depolariza
tion than 400 mu M glutamate, it was unlikely that the effects of both
glutamate and high [K+] on glial stellation were due to membrane depo
larization. Hypotonic treatment (120 mOsm) enhanced, whereas hypertoni
c treatment (520 mOsm) prevented, the glutamate reversal of glial stel
lation. Thus, glial swelling appeared to be a primary mechanism for th
e inhibitory effect of glutamate and high [K+] on glial stellation. Th
is mechanism could also explain the observation that glutamate inhibit
ed stellation induced by PMA, a PKC activator. Our data suggest that g
lutamate released from neurons during neuronal activity or pathology c
an be taken up by astrocytes and alter their morphology. Changes in gl
ial morphology may in turn affect the volume and composition of the ex
tracellular space and, as a result, neuronal activity. (C) 1994 Wiley-
Liss, Inc.