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Comparison of binding mechanisms at cholinergic, serotonergic, glycinergic and GABAergic receptors
Author(s) -
Aprison M.H.,
GalvezRuano E.,
Lipkowitz K.B.
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19960115)43:2<127::aid-jnr1>3.0.co;2-i
Subject(s) - glycine receptor , serotonergic , excitatory postsynaptic potential , ligand gated ion channel , neurotransmitter receptor , inhibitory postsynaptic potential , ion channel , receptor , gephyrin , neuroscience , neurotransmitter , cholinergic , chemistry , biology , glycine , amino acid , biochemistry , biophysics , serotonin
Abstract Employing computational methods and published data from molecular biological studies involving amino acid sequences in the polypeptide receptors, the authors studied and compared how two excitatory neurotransmitters, ACh and 5‐HT, and two inhibitory neurotransmitters, glycine and GABA, can bind to their respective recognition sites at CNS receptors. Models for each neurotransmitter interaction with specific amino acids are described and identified. Molecular mechanisms are identified that can explain how the binding process initiates ion flow through channels located within the postsynaptic membrane such that if the neurotransmitter is inhibitory, hyperpolarization occurs, and if excitatory, depolarization occurs. Although the theoretical work described indicates that there is a difference in molecular mechanisms operative at the anionic and cationic channels, and provides an explanation why the former is more specific, the molecular modeling data and the similarities of specific amino acids in the sequence in all four receptor polypeptides used to construct the four models support ACh, 5‐HT, glycine and GABA as being members of the same ligand‐gated ion channel superfamily. © 1996 Wiley‐Liss, Inc.