Pentobarbital modulatory effect on GABA binding sites in developing chick optic lobe

Abstract

Barbiturates are allosteric modulators of the CNS GABAA receptor, increasing [3H]-GABA binding to its receptor sites. In the present work we have studied the modulatory effect of the barbiturate pentobarbital on low-affinity GABA binding sites during ontogenetic development of the chick optic lobe. Our results indicate that [3H]-GABA binding enhancement by pentobarbital shows a differential profile during development, following a two-component enhancement model at early stages of development and a single-component enhancement model in the adult stage. Kinetic analysis performed at different stages of development showed that barbiturate enhancement was invariably due to an increase in [3H]-GABA binding affinity, while maximal binding capacity remained unchanged. Using GABA antagonists, picrotoxinin and bicuculline, convulsant sensitivity of high-affinity barbiturate modulatory sites was found at early stages. These data suggest that barbiturate action displays receptor heterogeneity during development, with high- and low-affinity modulatory sites only at early stages, while the high-affinity sites disappear between hatching and adulthood. Kinetic data indicate that both barbiturate modulatory sites are coupled to the GABAA receptor at early stages. The presence of high-affinity modulatory sites at early stages and at hatching suggests a major role during visual pathway maturation.

Development and localisation of GABAA receptor α1, α2, β2 and γ2 subunit mRNA in the chick optic tectum

“…Binding experiments carried out in our laboratory have demonstrated that both the BZ type I and type II are already expressed during development but with different temporal patterns. BZ type II binding sites are detected earlier than is the BZ type I (Gravielle and Fiszer de Plazas, 1995). These binding results are probably due to the changes in α 1 and α 2 expression described herein.…”

“…Nevertheless, the spatial pattern of expression, i.e., the distribution in the different layers during development, remains unknown. Differences in pharmacologic and biochemical properties of this receptor observed during normal development (Fiszer de Plazas et al, 1995; Pignataro et al, 1996; Viapiano and Fiszer de Plazas, 1998) or after injury at different embryonic days (Rodríguez Gil et al, 2000, 2002) could be attributed to changes in the subunit expression pattern.…”

Modulatory action of zinc on GABAA receptor complex during avian CNS development

“…In previous studies, we investigated the modulatory action of benzodiazepines, barbiturates, and neurosteroids on the GABA A receptor complex during chick optic lobe development by means of GABA and benzodiazepine binding and GABA-dependent chloride uptake experiments (Fiszer de Plazas and Mitridate de Novara, 1990;Fiszer de Plazas et al, 1995;Pignataro et al, 1996;Viapiano and Fiszer de Plazas, 1998;Gravielle et al, 1998). As in the case of zinc, all modulators analyzed act in an age-dependent manner, disclosing their maximal effects at early developmental stages and indicating a change in GABA A receptor sensitivity to these drugs during development.…”

Acute hypoxia differentially affects the γ‐aminobutyric acid type A receptor α1, α2, β2, and γ2 subunit mRNA levels in the developing chick optic tectum: Stage‐dependent sensitivity

“…Previous studies from our laboratory have established the pattern of expression, heterogeneity, modulation properties, and functionality of the GABA A R complex in the developing chick OT (Fiszer de Plazas and Mitridate de Novara, 1990; Fiszer de Plazas et al, 1995; Gravielle et al, 1998; Viapiano et al, 1998). We have also characterized the time of appearance and the temporal evolution of high‐ and low‐affinity GABA binding sites (Fiszer de Plazas et al, 1993).…”