The amino acid glycine is a major inhibitory neurotransmitter in the vertebrate CNS. Glycinergic synapses are particularly abundant in spinal cord and brain stem, but are also found in higher brain regions including the hippocampus. The inhibitory actions of glycine are potently blocked by the alkaloid strychnine, a convulsant poison in man and animals. Strychnine poisoning causes disinhibition of motoneurons and leads to hyperexcitability, convulsions and death through respiratory failure. In addition, it produces strong pain syndromes and hyperacuity of visual and auditory responses via disinhibition of sensory processing areas, i.e. dorsal horn of the spinal cord, cochlear nucleus, inferior colliculus and retina.

In addition to its inhibitory postsynaptic action, glycine also acts as an excitatory transmitter. First, it serves as a co-agonist of the NMDA-subtype of excitatory glutamate receptors; second, glycine has been shown to have excitatory effects on embryonic neurons. Like postsynaptic inhibition, this excitatory response is blocked by strychnine and results from an altered chloride equilibrium potential at early stages of development.

The strychnine-sensitive, postsynaptic glycine receptor (GlyR) is a ligand-gated chloride channel protein that belongs to the nicotinic acetylcholine receptor family. Purification and molecular cloning has shown that in adult mammals the GlyR is a pentameric transmembrane protein composed of α and β subunits. Pharmacologically distinct isoforms of the GlyR originate from the developmentally and regionally regulated expression of four distinct α subunit genes (α1-α4).

GlyRs containing the α1 subunit are highly expressed in adult spinal cord and brain stem, whereas α2 GlyRs represent the major embryonically and early postnatally expressed GlyR isoform. α3 GlyRs are highly concentrated in the dorsal horn of the spinal cord and have been shown to be the molecular substrate of prostaglandin E2-induced inflammatory pain sensitization. Expression of the GlyR α4 gene has so far only been detected in non-mammalian vertebrates.

Expression of cloned GlyR α subunits in Xenopus oocytes or mammalian cell lines creates glycine-gated strychnine-sensitive channels, which mimic GlyRs in primary spinal neurons in most of their pharmacological properties and may correspond to extrasynaptic receptors. Coexpression of the structural β subunit modifies the elementary conductance and channel blocker sensitivity of the GlyR chloride channel. In addition, the β subunit is essential for targeting the receptor to the synapse.

The pharmacology of the GlyR has been studied by different approaches. Besides glycine, the endogenous inhibitory amino acids β-alanine and taurine, as well as β-aminobutyric acid, act as full or partial agonists at the GlyR. Their relative potencies, however, differ between GlyR isoforms. Agonist activation of the GlyR is enhanced by neurosteroids and zinc ions. These ligands are thought to be important for modulating the efficacy of glycinergic synapses in vivo. In addition, tropeines, ethanol and anesthetics such as isofluorane and propofol potentiate glycine currents. These compounds constitute the major documented allosteric effectors of the GlyR.

The number of selective GlyR antagonists is still small. Strychnine constitutes the only high-affinity ligand suitable for GlyR binding studies. In addition, the steroid derivative RU5135, ω-phosphono-α-amino acid (PMBA) and 5,7-dichloro-4-hydroxyquinoline-3-carboyxylic acid (an analog of the NMDA receptor glycine site antagonist 5,7-dichlorokynurenate) antagonize glycine responses of cultured neurons and recombinant GlyRs. Cyanotriphenylborate, a negatively charged structural analog of the cation triphenylmethylphosphonium, has been shown to selectively antagonize GlyR α2 channels. All homo-oligomeric α subunit GlyRs are blocked by picrotoxinin.

Mutations in the GlyR α1 and β subunit genes underlie human startle disease (or hyperekplexia), a rare hereditary neuromotor disorder characterized by exaggerated startle responses to visual or acoustic stimuli. Severe forms cause prolonged myoclonic episodes which, in infants ("stiff baby syndrome"), may even be lethal due to sudden apnea.

The Table below contains accepted modulators and additional information. For a list of additional products, see the "Similar Products" section below.


PMBA: Phenylbenzene ω-phosphono-α-amino acid

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Becker L, von Wegerer J, Schenkel J, Zeilhofer H, Swandulla D, Weiher H. 2002. Disease-Specific Human Glycine Receptor ?1 Subunit Causes Hyperekplexia Phenotype and Impaired Glycine- and GABAA-Receptor Transmission in Transgenic Mice. J. Neurosci.. 22(7):2505-2512.
Dutertre S, Becker C, Betz H. 2012. Inhibitory Glycine Receptors: An Update. J. Biol. Chem.. 287(48):40216-40223.
Grewer C. 1999. Investigation of the ?1-Glycine Receptor Channel-Opening Kinetics in the Submillisecond Time Domain. Biophysical Journal. 77(2):727-738.
Harvey RJ, Betz H. 2000. Structure, Diversity, Pharmacology, and Pathology of Glycine Receptor Chloride Channels.479-497.
Harvey RJ. 2004. GlyR  3: An Essential Target for Spinal PGE2-Mediated Inflammatory Pain Sensitization. Science. 304(5672):884-887.
Laube B, Maksay G, Schemm R, Betz H. 2002. Modulation of glycine receptor function: a novel approach for therapeutic intervention at inhibitory synapses?. Trends in Pharmacological Sciences. 23(11):519-527.
Le-Corronc H, Rigo J, Branchereau P, Legendre P. 2011. GABAA Receptor and Glycine Receptor Activation by Paracrine/Autocrine Release of Endogenous Agonists: More Than a Simple Communication Pathway. Mol Neurobiol. 44(1):28-52.
Lynch JW. 2004. Molecular Structure and Function of the Glycine Receptor Chloride Channel. Physiological Reviews. 84(4):1051-1095.
Lynch JW. 2009. Native glycine receptor subtypes and their physiological roles. Neuropharmacology. 56(1):303-309.
Mascia MP, Machu TK, Harris RA. 1996. Enhancement of homomeric glycine receptor function by longchain alcohols and anaesthetics. 119(7):1331-1336.
Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, et al. 1997. Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors. Nature. 389(6649):385-389.
O'Shea SM. 2004. Propofol Restores the Function of "Hyperekplexic" Mutant Glycine Receptors in Xenopus Oocytes and Mice. Journal of Neuroscience. 24(9):2322-2327.
Perkins DI, Trudell JR, Crawford DK, Alkana RL, Davies DL. 2010. Molecular targets and mechanisms for ethanol action in glycine receptors. Pharmacology & Therapeutics. 127(1):53-65.
Rees MI. 2002. Hyperekplexia associated with compound heterozygote mutations in the beta-subunit of the human inhibitory glycine receptor (GLRB). 11(7):853-860.
Saitoh T, Ishida M, Maruyama M, Shinozaki H. 1994. A novel antagonist, phenylbenzene ?-phosphono-?-amino acid, for strychnine-sensitive glycine receptors in the rat spinal cord. 113(1):165-170.
Schmieden Vea. 1996. Pharmacology of the inhibitory glycine receptor: Agonist and antagonist actions of amino acid compounds.. Mol. Pharmacol. . 50, 1200-1206..
Yevenes GE, Zeilhofer HU. 2011. Allosteric modulation of glycine receptors. 164(2):224-236.

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