Molecular pharmacology of the glycine receptor chloride channel

Webb, TI and Lynch, JW (2007) Molecular pharmacology of the glycine receptor chloride channel. Current Pharmaceutical Design, 13 23: 2350-2367. doi:10.2174/138161207781368693

Author Webb, TI
Lynch, JW
Title Molecular pharmacology of the glycine receptor chloride channel
Journal name Current Pharmaceutical Design   Check publisher's open access policy
ISSN 1381-6128
Publication date 2007-01-01
Year available 2007
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2174/138161207781368693
Open Access Status
Volume 13
Issue 23
Start page 2350
End page 2367
Total pages 18
Editor Banks, WA
Place of publication Sharjah
Publisher Bentham Science Publ Ltd
Language eng
Subject C1
270104 Membrane Biology
670402 Diagnostics
Abstract The glycine receptor (GlyR) Cl- channel belongs to the cysteine-loop family of ligand-gated ion channel receptors. It is best known for mediating inhibitory neurotransmission in motor and sensory reflex circuits of the spinal cord, although glycinergic synapses are also present in the brain stem, cerebellum and retina. Extrasynaptic GlyRs are widely distributed throughout the central nervous system and they are also found in sperm and macrophages. A total of 5 GlyR subunits (alpha 1-4 and beta) have been identified. Embryonic receptors comprise alpha 2 homomers whereas adult receptors comprise predominantly alpha 1 beta heteromers in a 2:3 stoichiometry. Notably, the alpha 3 subunit is present in synaptic GlyRs that mediate inhibitory neurotransmission onto spinal nociceptive neurons. These receptors are specifically inhibited by inflammatory mediators, implying a role for alpha 3-containing GlyRs in inflammatory pain sensitisation. Because molecules-that increase GlyR current may have clinical potential as muscle relaxant and peripheral analgesic drugs, this review focuses on the molecular pharmacology of GlyR potentiating substances. Of all GlyR potentiating substances identified to date, we conclude that 5HT(3)R antagonists such as tropisetron offer the most promise as therapeutic lead compounds. However, one problem is that that virtually all known GlyR potentiating compounds, including tropisetron analogues, lack specificity for the GlyR. Another is that almost nothing is known about the pharmacological properties of alpha 3-containing GlyRs, which is the subtype of choice for targeting by novel antinociceptive agents. These issues need to be addressed before GlyR-specific therapeutics can be developed.
Keyword Pharmacology & Pharmacy
inhibitory neurotransmission
inflammatory pain
startle disease
cysteine-loop receptor family
therapeutic target
Rat Spinal Neurons
Gated Ion Channels
Nicotinic Acetylcholine-receptors
Ventromedial Hypothalamic Neurons
Inhibitory Synaptic-transmission
Induced Conformational-changes
Ligand-binding Site
Dorsal-horn Neurons
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes This document is a journal review.

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Created: Tue, 19 Feb 2008, 00:41:30 EST