Pentobarbital modulatory effect on GABA binding sites in developing chick optic lobe.
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.
Fiszer de Plazas
S
S
Instituto de Biología Celular y Neurociencias, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Viapiano
M S
MS
Mitridate de Novara
A
A
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development*; D002642:Chick Embryo; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D010424:Pentobarbital / Q000494:pharmacology*; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D054830:Sesterterpenes; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001640:Bicuculline; D018756:GABA Antagonists; D018757:GABA Modulators; D010424:Pentobarbital; D010852:Picrotoxin; D054830:Sesterterpenes; D005680:gamma-Aminobutyric Acid; C022961:picrotoxinin