The glycine receptor

Rajendra, Sundran; Lynch, Joseph W.; Schofield, Peter R.

doi:10.1016/s0163-7258(96)00163-5

Cited by 278 publications

(218 citation statements)

References 186 publications

Supporting

Mentioning

203

Contrasting

Unclassified

Order By: Relevance

“…It has been demonstrated that the GLY receptor has the typical pentameric structure, consisting of one of the highly homologous ligand-binding α subunits (α 1-4 subunits in mice, α 1-3 subunits in rats) and a β subunit that forms a chloride-selective transmembrane channel [1] . Our previous study showed that mRNA and protein for the α 1 and β subunits were detected in neonatal cardiomyocytes [23] .…”

Section: Discussionmentioning

confidence: 99%

“…Glycine (GLY), a nonessential amino acid, is well recognized as an inhibitory neurotransmitter in the central nervous system and functions via a GLY-gated chloride channel [1] . Recent studies have demonstrated that GLY has a wide spectrum of pharmacological effects, including suppressing endotoxininduced fever, antiinflammatory effects and direct cytoprotective actions [2,3] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glycine inhibits the LPS-induced increase in cytosolic Ca2+ concentration and TNFα production in cardiomyocytes by activating a glycine receptor

Wang

et al. 2009

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Previous studies have demonstrated that glycine (GLY) markedly reduces lipopolysaccharide (LPS)-induced myocardial injury. However, the mechanism of this effect is still unclear. The present study investigated the effect of GLY on cytosolic calcium concentration ([Ca 2+ ] c ) and tumor necrosis factor-α (TNFα) production in cardiomyocytes exposed to LPS, as well as whether the glycine-gated chloride channel is involved in this process. Methods: Neonatal rat cardiomyocytes were isolated, and the [Ca 2+ ] c and TNFα levels were determined by using Fura-2 and a Quantikine enzyme-linked immunosorbent assay, respectively. The distribution of the GLY receptor and GLY-induced currents in cardiomyocytes were also investigated using immunocytochemistry and the whole-cell patch-clamp technique, respectively. Results: LPS at concentrations ranging from 10 ng/mL to 100 µg/mL significantly stimulated TNFα production. GLY did not inhibit TNFα production induced by LPS at concentrations below 10 ng/mL but did significantly decrease TNFα release stimulated by 100 µg/mL LPS and prevented an LPS-induced increase in [Ca 2+ ] c , which was reversed by strychnine, a glycine receptor antagonist. GLY did not block the isoproterenol-induced increase in [Ca 2+ ] c , but did prevent the potassium chloride-induced increase in [Ca 2+ ] c in cardiomyocytes. Strychnine reversed the inhibition of the KCl-stimulated elevation in [Ca 2+ ] c by GLY. In chloride-free buffer, GLY had no effect on the dipotassium hydrogen phosphate-induced increase in [Ca 2+ ] c . Furthermore, GLY receptor α 1 and β subunit-immunoreactive spots were observed in cardiomyocytes, and GLY-evoked currents were blocked by strychnine. Conclusion: Cardiomyocytes possess the glycine-gated chloride channel, through which GLY prevents the increase in [Ca 2+ ] c and inhibits the TNFα production induced by LPS at high doses in neonatal rat cardiomyocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glycine inhibits the LPS-induced increase in cytosolic Ca2+ concentration and TNFα production in cardiomyocytes by activating a glycine receptor

Wang

et al. 2009

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…3) blunted LPSinduced increases in [Ca 2ϩ ] i in a dose-dependent manner, providing pharmacological evidence for the presence of a glycine-gated chloride channel in the Kupffer cell. The potencies of these two amino acids are similar in Kupffer cells; however, ␤-alanine is a more potent agonist than taurine in the central nervous system [26,45].…”

Section: The Glycine-gated Chloride Channel In Kupffer Cells Is Sensimentioning

confidence: 99%

Taurine blunts LPS-induced increases in intracellular calcium and TNF-α production by Kupffer cells

Seabra

Stachlewitz

Thurman

1998

Journal of Leukocyte Biology

View full text Add to dashboard Cite

“…Glycine receptors belong to a superfamily of ligand-gated chloride channels that include GABA A 1 receptors, GABA C receptors, and glutamate-gated chloride channels (1). In native tissue, glycine receptors exist as either ␣ homomers or ␣␤ heteromers (1).…”

mentioning

confidence: 99%

“…Each subunit is made up of a large extracellular N-terminal region, four transmembrane domains (TM), and a large cytoplasmic domain; TMII forms the channel lumen (2). Glycine receptors are targets of therapeutics such as anesthetics as well as toxins like the central nervous system convulsant picrotoxin (1).…”

mentioning

confidence: 99%

Identification of a Novel Residue within the Second Transmembrane Domain That Confers Use-facilitated Block by Picrotoxin in Glycine α1 Receptors

Dibas

Gonzales

Das

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

The central nervous system convulsant picrotoxin (PTX) inhibits GABA A and glutamate-gated Cl ؊ channels in a use-facilitated fashion, whereas PTX inhibition of glycine and GABA C receptors displays little or no use-facilitated block. We have identified a residue in the extracellular aspect of the second transmembrane domain that converted picrotoxin inhibition of glycine ␣1 receptors from non-use-facilitated to usefacilitated. In wild type ␣1 receptors, PTX inhibited glycine-gated Cl ؊ current in a competitive manner and had equivalent effects on peak and steady-state currents, confirming a lack of use-facilitated block. Mutation of the second transmembrane domain 15-serine to glutamine (␣1(S15Q) receptors) converted the mechanism of PTX blockade from competitive to non-competitive. However, more notable was the fact that in ␣1(S15Q) receptors, PTX had insignificant effects on peak current amplitude and dramatically enhanced current decay kinetics. Similar results were found in ␣1(S15N) receptors. The reciprocal mutation in the ␤2 subunit of ␣1␤2 GABA A receptors (␣1␤2(N15S) receptors) decreased the magnitude of use-facilitated PTX inhibition. Our results implicate a specific amino acid at the extracellular aspect of the ion channel in determining use-facilitated characteristics of picrotoxin blockade. Moreover, the data are consistent with the suggestion that picrotoxin may interact with two domains in ligand-gated anion channels.Glycine receptors belong to a superfamily of ligand-gated chloride channels that include GABA A 1 receptors, GABA C receptors, and glutamate-gated chloride channels (1). In native tissue, glycine receptors exist as either ␣ homomers or ␣␤ heteromers (1). They comprise five subunits (usually three ␣ subunits and two ␤ subunits) arranged asymmetrically around the ion pore. Each subunit is made up of a large extracellular N-terminal region, four transmembrane domains (TM), and a large cytoplasmic domain; TMII forms the channel lumen (2). Glycine receptors are targets of therapeutics such as anesthetics as well as toxins like the central nervous system convulsant picrotoxin (1).Picrotoxin inhibits all known anionic ligand-gated Cl Ϫ channels (3-5). The mechanism of action and the exact location of picrotoxin binding are still unknown (6 -12). However, several studies have indicated that TMII is the probable site for picrotoxin action (6, 13-22) (Fig. 1). For example, the TMII of the glycine ␤ subunit was found to be responsible for conferring resistance to picrotoxin in heteromeric glycine ␣ n ␤ receptors (n ϭ 1-3) (6). Subsequent work has defined the existence of a phenylalanine residue at the 6Ј position of the TMII glycine ␤ subunit in conferring insensitivity to picrotoxin (16). In addition, other TMII residues (2Ј and 19Ј) have also been implicated directly or indirectly in the mechanism by which picrotoxin inhibits these channels (13, 15,16). The mutations at positions 2Ј and 19Ј have been shown to affect the type of the inhibition (competitive versus non-competitive) by picrotoxin ...

show abstract

The glycine receptor

Cited by 278 publications

References 186 publications

Glycine inhibits the LPS-induced increase in cytosolic Ca2+ concentration and TNFα production in cardiomyocytes by activating a glycine receptor

Glycine inhibits the LPS-induced increase in cytosolic Ca2+ concentration and TNFα production in cardiomyocytes by activating a glycine receptor

Taurine blunts LPS-induced increases in intracellular calcium and TNF-α production by Kupffer cells

Identification of a Novel Residue within the Second Transmembrane Domain That Confers Use-facilitated Block by Picrotoxin in Glycine α1 Receptors

Contact Info

Product

Resources

About