β‐Alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus <i>in vitro</i>

Mori, Masahiro; Gähwiler, Beat H.; Gerber, Urs

doi:10.1113/jphysiol.2001.013147

Cited by 197 publications

(152 citation statements)

References 49 publications

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“…Indeed, we found that endogenous accumulation of glycine by GlyT1 antagonists induced an STN-sensitive tonic current in CA1 pyramidal neurons ( Figure 5). The reported existence of GlyRs containing homomeric a2 subunits in the hippocampus (Chattipakorn and McMahon, 2002;Mori et al, 2002;Thio et al, 2003;Yoon et al, 1998) may underlie this tonic current. In general, functional consequences of the tonic inhibition are not well understood.…”

Section: Glycine Accumulation Reduces Overall Excitabilitymentioning

confidence: 93%

“…Then we tested the dose-response effects of glycine on the E-S curve and found that it was only effective at the highest concentration tested, 1 mM (0.1 mM, 5.1273.69%, t ¼ 1.4, df ¼ 13, p40.05; 0.3 mM, 3.3972.12%, t ¼ 1.6, df ¼ 9, p40.05; 1 mM, 7.5871.4%, t ¼ 5.8, df ¼ 6, po0.01; Figure 2b and d). We also examined the effect of an endogenous GlyR agonist in the hippocampus, taurine (1 mM, a concentration that does not affect GABA A Rs) (Mori et al, 2002;Wu and Xu, 2003), to further confirm the involvement of GlyRs. A rightward shift of the E-S curve was evident after addition of taurine (14.9774.65%, t ¼ 3.3, df ¼ 6, po0.05; Figure 2c and d).…”

Section: Effects Of Glyr Agonist and Antagonist On E-s Coupling In Himentioning

confidence: 99%

“…Electrophysiological (Thio et al, 2003;Chattipakorn and McMahon, 2003), immunocytochemical (Becker et al, 1993), and in situ hybridization studies (Malosio et al, 1991) have shown that functional GlyRs are also present in many regions of developing and mature brain, including the hippocampus, where they are expressed by CA1 pyramidal cells and interneurons. Although no glycinergic synaptic transmission has been found in the hippocampus (Mody et al, 1994), accumulating evidence shows the presence of non-synaptic GlyRs containing at least a2 subunit (Chattipakorn and McMahon, 2002;Mori et al, 2002;Thio et al, 2003;Yoon et al, 1998). Thus, GlyRs are likely to have profound effects on cortical function, and may play a fundamental role in modulating hippocampal excitability.…”

Section: Introductionmentioning

confidence: 99%

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Glycine Uptake Regulates Hippocampal Network Activity via Glycine Receptor-Mediated Tonic Inhibition

Zhang

Gong

et al. 2007

Neuropsychopharmacol

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Functional glycine receptors (GlyRs) are enriched in the hippocampus, but their role in hippocampal function remains unclear. Since the concentration of ambient glycine is determined by the presence of powerful glycine transporter (GlyT), we blocked the reuptake of glycine in hippocampal slices to examine the role of GlyRs. Antagonists of GlyT type 1 (GlyT1) but not that of GlyT type 2 (GlyT2) induced excitatory postsynaptic potential (EPSP)-spike depression, which was reversed by the specific GlyR antagonist strychnine. Moreover, endogenously elevating the glycine concentration with the GlyT1 antagonists facilitated NMDA receptor-dependent longterm potentiation induction, and elicited a strychnine-sensitive chloride current. In addition, impairment of glial function with fluoroacetate blocked the effect of GlyT1 antagonists on the EPSP-spike curve. Furthermore, pretreatment with sarcosine was effective in controlling pentylenetetrazol-induced seizures. These results indicate an essential role of GlyTs in fine-tuning tonic activation of GlyRs and suggest a potential role of GlyR-dependent EPSP-spike depression in hippocampal network stability.

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Section: Glycine Accumulation Reduces Overall Excitabilitymentioning

confidence: 93%

Section: Effects Of Glyr Agonist and Antagonist On E-s Coupling In Himentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glycine Uptake Regulates Hippocampal Network Activity via Glycine Receptor-Mediated Tonic Inhibition

Zhang

Gong

et al. 2007

Neuropsychopharmacol

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“…2a). Because taurine has been suggested as an endogenous ligand for GlyR (3,22), we also tested the effect of GB on taurine (5 mM)-induced responses (Fig. 2b).…”

Section: Resultsmentioning

confidence: 99%

Terpene Trilactones from Ginkgo biloba Are Antagonists of Cortical Glycine and GABAA Receptors

Ivic¹,

Sands

Fishkin

et al. 2003

Journal of Biological Chemistry

110

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Glycine and ␥-aminobutyric acid, type A (GABA A ) receptors are members of the ligand-gated ion channel superfamily that mediate inhibitory synaptic transmission in the adult central nervous system. During development, the activation of these receptors leads to membrane depolarization. Ligands for the two receptors have important implications both in disease therapy and as pharmacological tools. Terpene trilactones (ginkgolides and bilobalide) are unique constituents of Ginkgo biloba extracts that have various effects on the central nervous system. We have investigated the relative potency of these compounds on glycine and GABA A receptors. We find that most of the ginkgolides are selective and potent antagonists of the glycine receptor. Bilobalide, the single major component in G. biloba extracts, also reduces glycine-induced currents, although to a lesser extent. Both ginkgolides and bilobalide inhibit GABA A receptors, with bilobalide demonstrating a more potent effect. Additionally, we provide evidence that open channels are required for glycine receptor inhibition by ginkgolides. Finally, we employ molecular modeling to elucidate the similarities and differences in the structure of the terpene trilactones to account for the pharmacological properties of these compounds and demonstrate a striking similarity between ginkgolides and picrotoxinin, a GABA A and recombinant glycine ␣-homomeric receptor antagonist.Glycine and ␥-aminobutyric acid receptors (GlyRs 1 and GABA A Rs) are anion-selective ligand-gated ion channels, which together with the cation-selective nicotinic acetylcholine and serotonin receptors constitute a superfamily of membrane receptors that mediate fast chemical synaptic transmission in the nervous system. These receptors share several structural similarities, i.e. a pentameric arrangement of subunits, each composed of four transmembrane domains (M1-M4) and an extracellular 15-residue Cys-loop motif-bearing N terminus (1, 2).

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“…In addition, ssGlyRs can be gated by the β-amino acids, including β-alanine and taurine, which act as partial agonists [45]. Like glycine, taurine and β-alanine are abundant in the central nervous system and could also serve as native agonists for ssGlyRs in some brain regions [34].…”

Section: Introductionmentioning

confidence: 99%

Strychnine and taurine modulation of amygdala-associated anxiety-like behavior is ‘state’ dependent

McCool¹,

Chappell²

2007

Behavioural Brain Research

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Strychnine-sensitive glycine receptors are expressed in many adult forebrain regions, yet the biological function of these receptors outside the spinal cord/brainstem is poorly understood. We have recently shown that rat lateral/basolateral amygdala neurons express strychnine-sensitive glycine-gated currents whose pharmacological and molecular characteristics are consistent with those established for classic ligand-gated chloride channels. The current studies were undertaken to establish the behavioral role, if any, of these strychnine-sensitive glycine receptors. Adult LongEvans male rats were implanted with guide cannulae targeted at the lateral amygdala and were microinjected with standard artificial cerebrospinal fluid with or without various doses of strychnine or taurine. Anxiety-like behaviors were assessed with the elevated plus-maze or the light/dark box. In the elevated plus maze, strychnine decreased closed-arm time and increased open-arm time, suggestive of an anxiolytic effect. Similarly, strychnine produced a modest anxiolytic effect in the light/dark box. Post-hoc analysis of 'open-arm' time and 'light-side' time indicated that aCSF-treated animals were distributed into two apparent groups that displayed either high or low amounts of anxiety-like behavior in a given apparatus. Surprisingly, the pharmacological effects of both strychnine and taurine in these assays were dependent upon a given animal's behavioral phenotype. Together, these findings are significant because they suggest that the basal 'emotional state' of the animal could influence the behavioral outcome associated with drug application directly into the lateral/basolateral amygdala. Furthermore, our findings also suggest that compounds acting at amygdala strychnine-sensitive glycine receptors may actively modulate this basal anxiety-like state.

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β‐Alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro

Cited by 197 publications

References 49 publications

Glycine Uptake Regulates Hippocampal Network Activity via Glycine Receptor-Mediated Tonic Inhibition

Glycine Uptake Regulates Hippocampal Network Activity via Glycine Receptor-Mediated Tonic Inhibition

Terpene Trilactones from Ginkgo biloba Are Antagonists of Cortical Glycine and GABAA Receptors

Strychnine and taurine modulation of amygdala-associated anxiety-like behavior is ‘state’ dependent

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