Characterization of an inhibitory receptor in rat hippocampus: a microiontophoretic study using con‐formationally restricted amino acid analogues
M. Segal,K. Sims,E. Smissman +2 more
TLDR
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.Abstract:
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 A). 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 angstroms.read more
Citations
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Localization of transmitter candidates in the brain: the hippocampal formation as a model
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Pharmacological characterization of different types of GABA and glutamate receptors in vertebrates and invertebrates.
A Nistri,A Constanti +1 more
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High affinity GABA receptors — Autoradiographic localization
TL;DR: The distribution of the high affinity gamma-aminobutyric acid (GABA) receptor labeled by [3H]muscimol, has been studied in the rat brain by light microscopic autoradiography in correlation with the known distribution of GABAergic terminals and the presence of inhibitory GABAergic mechanisms.
References
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Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat.
TL;DR: The proposal is made that this amino acid, released at inhibitory axodendritic or axo-axonic synapses, is responsible for the prolonged inhibition of spinal motoneurones by repetitive impulses in afferent fibres (‘presynaptic’ inhibition).
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The hyperpolarization of spinal motoneurones by glycine and related amino acids.
TL;DR: The results indicate that glycine may be a major spinal inhibitory transmitter, in which case strychnine affects spinal postsynaptic inhibition by limiting the action of glycine upon subsynaptic inhibitory receptors.
Journal ArticleDOI
The action of norepinephrine in the rat hippocampus. I. Iontophoretic studies.
Menahem Segal,Floyd E. Bloom +1 more
TL;DR: It is suggested that norepinephrine is a neurotransmitter candidate in the hippocampus and that it may act via the cyclic AMP system.
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