Ms. Viapiano et al., NEUROSTEROID MODULATION OF GABA BINDING-SITES IN DEVELOPING AVIAN CENTRAL-NERVOUS-SYSTEM, Neurochemistry international, 32(3), 1998, pp. 291-298
Our aim was to examine the effect of the potent neurosteroid 3 alpha-h
ydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-P) on [H-3]-GABA bindin
g to its receptor sites in the chick optic lobe. Binding was performed
on synaptic membranes isolated at different stages of development and
two different membrane preparation procedures were applied to expose
high and low affinity GABA binding sites. The addition of 3 alpha,5 al
pha-P was shown to increase [H-3]-GABA binding in an age-and concentra
tion-dependent manner. Maximal stimulation for low affinity GABA bindi
ng sites was observed at hatching (130% enhancement), in fresh-washed
as well as in frozen membranes. Saturation analysis performed on both
membrane types disclosed that 3 alpha,5 alpha-P increases the affinity
of low affinity GABA binding sites without altering their maximal bin
ding capacity. On the other hand, the augmenting effect at high affini
ty sites, displayed only in frozen membranes, was roughly 50% for all
developmental stages. However, their saturation binding parameters rem
ained unaltered in the presence of the steroid, suggesting that stimul
ation of such sites seems due to interference exerted by the low affin
ity site population. Findings indicate that 3 alpha,5 alpha-P acts as
an allosteric modulator only for low affinity GABA binding sites, disp
laying an age-dependent profile probably related to plastic events dur
ing visual pathway development. (C) 1998 Elsevier Science Ltd. All rig
hts reserved.