Behavioral and biochemical analysis of GABA-mediated inhibition in the early chick embryo.
Exogenous gamma-aminobutyric acid (GABA) decreased spontaneous motility in 4-, 6-, 7-, 9-, and 13-day chick embryos; the younger embryos were more sensitive. Neither the positional isomers of GABA, alpha-aminobutyric acid (AABA) and beta-aminobutyric acid, nor the principle GABA catabolite, succinic acid, decreased motility in 4-day embryos. Several semi-rigid GABA analogues decreased motility in 4-day embryos with a potency that paralleled their effectiveness in displacing [3H]GABA in ligand-binding studies. The effects of AABA and GABA on hind-limb motility were quantitatively similar in thoracic spinal and sham-operated 7-day embryos. Bicuculline and picrotoxin elicited absolute motility increases at 6, 7 and 9 days of incubation. Picrotoxin and two bicyclophosphate GABA antagnoists elicited relative motility increases while bicuculline elicited an absolute motility increase at 4 days. The two bicyclophosphates increased motility with a potency that paralleled their electrophysiological effectiveness. L-Glutamic acid decarboxylase (GAD) activity was detected in the embryonic lumbar spinal cord at all ages examined (3--7 days) using a new radiometric cation-exchange method. Gamma-Aminobutyric acid transaminase (GABA-T) activity was detected in the lumbar spinal cord at the earliest age examined (day 5). Both GAD and GABA-T activity were detected at earlier ages than previously reported. GABA receptors, and the enzymes necessary for the synthesis and degradation of GABA, all appear to be present at (or before) the onset of spontaneous motility. GABA-mediated transmission appears to be present at 6 days and perhaps as early as 4 days.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism*; D000367:Age Factors; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D013386:Succinates / Q000494:pharmacology; D000637:Transaminases / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D000612:4-Aminobutyrate Transaminase; D000613:Aminobutyrates; D002262:Carboxy-Lyases; D005968:Glutamate Decarboxylase; D009118:Muscimol; D010852:Picrotoxin; D017981:Receptors, Neurotransmitter; D013386:Succinates; D000637:Transaminases; D005680:gamma-Aminobutyric Acid