TY - JOUR
T1 - Identification of novel specific allosteric modulators of the glycine receptor using phage display
AU - Tipps, Megan E.
AU - Lawshe, Jessica E.
AU - Ellington, Andrew D.
AU - Mihic, S. John
PY - 2010/7/23
Y1 - 2010/7/23
N2 - The glycine receptor (GlyR) is a member of the Cys-loop superfamily of ligand-gated ion channels and the major mediator of inhibitory neurotransmission in the spinal cord and brainstem. Many allosteric modulators affect the functioning of members of this superfamily, with some such as benzodiazepines showing great specificity and others such as zinc, alcohols, and volatile anesthetics acting on multiple members. To date, no potent and efficacious allosteric modulator acting specifically at the GlyR has been identified, hindering both experimental characterization of the receptor and development of GlyR-related therapeutics. We used phage display to identify novel peptides that specifically modulate GlyR function. Peptide D12-116 markedly enhanced GlyR currents at low micromolar concentrations but had no effects on the closely related γ-aminobutyric acid type A receptors. This approach can readily be adapted for use with other channels that currently lack specific allosteric modulators.
AB - The glycine receptor (GlyR) is a member of the Cys-loop superfamily of ligand-gated ion channels and the major mediator of inhibitory neurotransmission in the spinal cord and brainstem. Many allosteric modulators affect the functioning of members of this superfamily, with some such as benzodiazepines showing great specificity and others such as zinc, alcohols, and volatile anesthetics acting on multiple members. To date, no potent and efficacious allosteric modulator acting specifically at the GlyR has been identified, hindering both experimental characterization of the receptor and development of GlyR-related therapeutics. We used phage display to identify novel peptides that specifically modulate GlyR function. Peptide D12-116 markedly enhanced GlyR currents at low micromolar concentrations but had no effects on the closely related γ-aminobutyric acid type A receptors. This approach can readily be adapted for use with other channels that currently lack specific allosteric modulators.
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U2 - 10.1074/jbc.M110.130815
DO - 10.1074/jbc.M110.130815
M3 - Article
C2 - 20501662
AN - SCOPUS:77954919617
SN - 0021-9258
VL - 285
SP - 22840
EP - 22845
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 30
ER -