Structure and Expression of Inhibitory Glycine Receptors

Betz, Heinrich; Langosch, Dieter; Hoch, Werner; Prior, Peter; Pribilla, I.; Kuhse, Jochen; Schmieden, Volker; Malosio, Maria Luisa; Matzenbach, B.; Holzinger, F.; Kuryatov, Alexander; Schmitt, Bertram; Maulet, Yves; Becker, Cord Michael

doi:10.1007/978-1-4684-5907-4_37

Cited by 30 publications

(19 citation statements)

References 36 publications

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“…The GlyR is a pentamer, and different subtypes of GlyRs may have different subunit compositions (22)(23)(24). Our data show that Zn 2ϩ selectively modulates the strychnine-sensitive GlyRs but not the DCKA-sensitive GlyRs.…”

Section: Znmentioning

confidence: 73%

Modulation of glycine receptors in retinal ganglion cells by zinc

Han

Wu²

1999

Proc. Natl. Acad. Sci. U.S.A.

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Effects of zinc, an endogenous neuromodulator in the central nervous system, on glycine receptors (GlyRs) in retinal ganglion cells were investigated by using the whole-cell voltage-clamp technique. Zn 2؉ at low concentration (<2 M) potentiated the glycine-induced chloride current and at higher concentration (>10 M) suppressed it. This biphasic regulatory action of zinc acted selectively on the fast component of the glycine-induced current mediated by the strychnine-sensitive GlyRs, but not on the slow component mediated by the 5,7-dichlorokynurenic acid-sensitive GlyRs. Dose-response studies showed that 1 M Zn 2؉ increased the maximum glycine response (I ؔ ) and shifted the EC 50 to the left, suggesting that Zn 2؉ at low concentrations acts as an allosteric activator of the strychnine-sensitive GlyRs. Zn 2؉ at a concentration of 100 M did not alter I ؔ and shifted the EC 50 to the right, indicating that Zn 2؉ at high concentrations acts as a competitive inhibitor of the GlyRs. Physiological functions of zinc modulation of GlyRs in retinal ganglion cells are discussed.

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Section: Znmentioning

confidence: 73%

Modulation of glycine receptors in retinal ganglion cells by zinc

Han

Wu²

1999

Proc. Natl. Acad. Sci. U.S.A.

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“…Glycine receptors are rich in spinal cord and brain stem, whereas 5-HT 3 receptors exist peripheral nervous systems such as intestines and brain stem area related with emesis in central nervous system. 24,25) Although we could not clearly answer the roles of quercetin and its glycosides that inhibit both ligand-gated ion channel activities in nervous systems, it seems that quercetin and its glycosides might exert their effects with differential manners in different regions of nervous systems.…”

Section: Discussionmentioning

confidence: 99%

Differential Regulations of Quercetin and Its Glycosides on Ligand-Gated Ion Channels

Lee

Pyo

Lee

et al. 2008

Biological & Pharmaceutical Bulletin

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The glycine and 5-hydroxytryptamine type 3 (5-HT 3 ) receptors are the superfamily of ligand-gated ion channel receptors with cysteine loop and share a structural similarity with nicotinic acetylcholine and g-aminobutyric acid A (GABA A ) receptors.1) The glycine receptor is predominantly expressed in spinal cord, brain stem and other regions of the central nervous system.2) The activations of glycine receptor in these regions mediate post-synaptic inhibitions for reflex responses, voluntary motor control, and the processing of sensory signals, 2) since the glycine receptor forms a chloridepermeable and -selective transmembrane channel. Thus, the glycine receptor is responsible for fast inhibitory synaptic transmissions. 3)On the other hand, 5-HT 3 receptor mediates rapid and transient membrane depolarizing effects of 5-HT in the central and peripheral nervous system like nicotinic acetylcholine receptors.1) 5-HT 3A receptor composes of a N-terminal domain, four transmembrane domains (TM1 to TM4), and an intracellular domain and finally homomeric pentamers of each subunit consist of 5-HT 3 receptor as glycine receptor does.4) The physiological and pathological roles of 5-HT 3 receptor involve pain transmission, analgesia, vomiting, and mood disorders and drug abuse. 5)Recently, we have reported that quercetin regulates glycine and 5-HT 3A receptor channel activities through interaction with amino acid residues existing in pore region of transmembrane domain 2 and N-terminal of pre-transmembrane domain 1, respectively. 6,7) Interestingly, in fruits and vegetables quercetin naturally exists as monomer-(quercetin-3-Orhamoside), (Rham1) dimer-(Rutin), or trimer-glycosides [quercetin-3-(2 G -rhamnosylrutinoside)] (Rham2) at carbon-3 and other glycosidic forms.8,9) When animal or human intakes fruits or vegetables, the dietary quercetin glycosides are metabolized to quercetin or conjugated with glucose or sulfate. A line of evidence showed that quercetin glycosides in addition to quercetin also exert their physiological or pharmacological effects. 8,9) However, until now little is known on how quercetin glycosides affect on the regulations of glycine and 5-HT 3A receptor channel activities.In the present study, we examined the effects of quercetin glycosides on the human glycine a1 receptor and mouse 5-HT 3A receptor channel activities expressed in Xenopus oocytes using a two-electrode voltage clamp technique. We found that applications of quercetin and its glycosides reversibly inhibited glycine-induced current (I Gly ) in order of quercetinϾRutinՆRham1ϾRham2. In oocytes expressing 5-HT 3A receptor, applications of quercetin and its glycosides also reversibly inhibited 5-HT-induced current (I 5-HT ) in order of Rham2ՆquercetinϾRutinϭRham1. The inhibitions of I Gly by quercetin glycosides were not competitive and voltagesensitive, whereas the inhibitions of I 5-HT by quercetin glycosides were competitive and voltage-insensitive manners. These results indicate that quercetin glycosides might regulate the human glycine ...

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“…The channel is comprised of three distinct protein subunits: a 48-kDa h subunit, a 58-kDa i subunit, and a 93-kDa cytoplasmic anchoring protein, gephyrin [12,13]. Three different isoforms of the h subunit have been identified and cloned from rat: the original purified 48-kDa h subunit (h1), a 49-kDa h2 subunit [32], and a 50-kDa h3 subunit [33,34]. Moreover, homologues of the h1, h2, and the i subunits of the GlyR have been identified and cloned from human and mouse spinal cord [35][36][37][38][39][40].…”

Section: Characteristics Of Glycine-gated Chloride Channelsmentioning

confidence: 99%

“…Recently, a fourth h subunit has been identified (denoted h4) by Matzenbach et al [41]. For rat, mouse, and human, the h subunits share striking sequence identity with each other and with subunits of the nicotinic acetylcholine receptor (nAchR) and the GABA type A receptor (GABA A R), as well as several other ligand-gated chloride channels [1,33]. The GlyR is comprised of five subunits, formed from either h subunits or a combination of h and i subunits, arranged in a pentameric complex which spans the cell membrane.…”

Section: Characteristics Of Glycine-gated Chloride Channelsmentioning

confidence: 99%

Glycine: a new anti-inflammatory immunonutrient

Wheeler

Ikejema

Enomoto

et al. 1999

Cellular and Molecular Life Sciences (CMLS)

157

124

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The mechanism of the immunosuppressive effects of glycine and its pathophysiological applications are discussed in this review. Glycine has been well characterized in spinal cord as an inhibitory neurotransmitter which activates a glycine-gated chloride channel (GlyR) expressed in postsynaptic membranes. Activation of the channel allows the influx of chloride, preventing depolarization of the plasma membrane and the potentiation of excitatory signals along the axon. Glycine has recently been shown to have similar inhibitory effects on several white blood cells, including hepatic and alveolar macrophages, neutrophils, and lymphocytes. Pharmacological analysis using a GlyR antagonist strychnine, chloride-free buffer, and radiolabeled chloride has provided convincing evidence to support the hypothesis that many white blood cells contain a glycine-gated chloride channel with properties similar to the spinal cord GlyR. Molecular analysis using reverse transcription-polymerase chain reaction and Western blotting has identified the mRNA and protein for the beta subunit of the GlyR in total RNA and purified membrane protein from rat Kupffer cells. Dietary glycine is protective in rat models against endotoxemia, liver ischemia-reperfusion, and liver transplantation, most likely by inactivating the Kupffer cell via this newly identified glycine-gated chloride channel. Glycine also prevents the growth of B 16 melanomas cell in vivo. Moreover, dietary glycine is protective in the kidney against cyclosporin A toxicity and ischemia-reperfusion injury. Glycine may be useful clinically for the treatment of sepsis, adult respiratory distress syndrome, arthritis, and other diseases with an inflammatory component.

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Structure and Expression of Inhibitory Glycine Receptors

Cited by 30 publications

References 36 publications

Modulation of glycine receptors in retinal ganglion cells by zinc

Modulation of glycine receptors in retinal ganglion cells by zinc

Differential Regulations of Quercetin and Its Glycosides on Ligand-Gated Ion Channels

Glycine: a new anti-inflammatory immunonutrient

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