COMPARISON OF BINDING MECHANISMS AT CHOLINERGIC, SEROTONERGIC, GLYCINERGIC AND GABAERGIC RECEPTORS

Employing computational methods and published data from molecular biol ogical studies involving amino acid sequences in the polypeptide recep tors, the authors studied and compared how two excitatory neurotransmi tters, 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 aci ds are described and identified. Molecular mechanisms are identified t hat can explain how the binding process initiates ion flow through cha nnels located within the postsynaptic membrane such that if the neurot ransmitter is inhibitory, hyperpolarization occurs, and if excitatory, depolarization occurs, Although the theoretical work described indica tes that there is a difference in molecular mechanisms operative at th e anionic and cationic channels, and provides an explanation why the f ormer is more specific, the molecular modeling data and the similariti es of specific amino acids in the sequence in all four receptor polype ptides used to construct the four models support ACh, 5-HT, glycine an d GABA as being members of the same ligand-gated ion channel superfami ly, (C) 1996 Wiley-Liss, Inc.