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

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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.