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CHARACTERIZATION OF AN INHIBITORY RECEPTOR IN RAT HIPPOCAMPUS: A MICROIONTOPHORETIC STUDY USING CON‐FORMATIONALLY RESTRICTED AMINO ACID ANALOGUES
Author(s) -
SEGAL M.,
SIMS K.,
SMISSMAN E.
Publication year - 1975
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1975.tb06927.x
Subject(s) - picrotoxin , bicuculline , strychnine , amino acid , inhibitory postsynaptic potential , glycine , nipecotic acid , gaba receptor antagonist , chemistry , glycine receptor , gamma aminobutyric acid , hippocampal formation , alanine , gabaa receptor , stereochemistry , receptor , biochemistry , biophysics , biology , neurotransmitter , neuroscience
1 Pyramidal cells in rat hippocampus were used to study the molecular dimensions of a receptor for inhibitory amino acids in the central nervous system. The inhibitory potencies of γ‐aminobutyrate (GABA), β‐alanine and glycine were compared by standard microiontophoretic techniques. Subsequently, rigid cyclopentane and cyclohexane amino acid analogues were applied by iontophoresis and their relative efficacies were compared with those of the naturally occurring amino acids. 2 GABA was the most effective of the small aliphatic amino acids in producing inhibition of the firing of hippocampal pyramidal neurones. β‐Alanine was less effective and glycine was the least effective. GABA‐induced inhibition was antagonized by concurrent iontophoresis of picrotoxin or bicuculline, whereas strychnine did not antagonize GABA inhibition. 3 The ability of the series of substituted aminocyclopentane and aminocyclohexane carboxylic acids to produce inhibition of pyramidal cells was a direct function of the separation of amino and carboxylic acid groups. In both series of the cyclic amino acids the most potent inhibition was demonstrated when the spatial separation was similar to that of the extended GABA molecule (4.74 Å). Additionally, the inhibition of hippocampal pyramidal cells by (±)‐ cis ‐3‐amino‐cyclopentanecarboxylic acid, like that produced by GABA, could be blocked by simultaneous application of picrotoxin or bicuculline, but not by strychnine. 4 The present results suggest that the physiologically active conformation of GABA is the fully extended molecule, and additionally indicate that one dimension of the postsynaptic receptor site is within the range of 4.2 to 4.8 ångströms.