Involvement of GABA receptors in the regulation of neurite growth in cultured embryonic chick tectum.

Modulation of neurite growth by gamma-aminobutyric acid (GABA) and several agonists and antagonists to its receptors was analysed in neuronal cultures of embryonic chick tectum and rat cerebellum, respectively, using morphometric methods. In each case, modulation of growth by GABA was similar in both types of neurons. However, data on neurite elongation suggest differential effects depending on the culture medium used. In serum-containing medium GABA stimulated neurite growth. In serum-free, defined medium the opposite effect was observed, i.e. GABA inhibited neurite elongation in tectal as well as in cerebellar cultures. When agonists of the GABAA-receptor were employed stimulation of neurite outgrowth was observed in serum-supplemented medium but not in serum-free medium. These ligands could not influence the inhibition of neurite growth caused by GABA. In contrast, the GABAB-receptor agonist (-)baclofen inhibited neurite elongation in serum-free medium without affecting cells in the presence of serum. Phaclofen, a GABAB-receptor antagonist, induced quite the opposite effect. It stimulated neurite elongation in serum-free culture conditions and prevented the inhibition induced by GABA in a concentration-dependent manner. In serum-supplemented medium it had no effect. The data suggest that GABAA-receptors may be involved in the GABA-induced neurite elongation in serum-supplemented medium only, although this subtype of receptors is present in serum-free conditions as well as revealed in binding studies using [3H]muscimol. Whether GABAB-receptors and/or as yet undefined mechanisms are responsible for the different action of GABA in serum-free medium is subject of further investigations.