New insights in endogenous modulation of ligand-gated ion channels: Histamine is an inverse agonist at strychnine sensitive glycine receptors

Kletke, Olaf; Sergeeva, Olga A.; Lorenz, P.; Oberland, Sonja; Meier, Jochen C.; Hatt, Hanns; Gisselmann, Günter

doi:10.1016/j.ejphar.2013.04.002

Cited by 11 publications

(9 citation statements)

References 38 publications

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“…The high plasma histidine in the benzene-exposed groups may be caused by a diminished activity of histidine decarboxylase (HDC) [35], which results in inhibiting decarboxylation of histidine to histamine in benzene-exposed mice. Histamine is an amine derived by enzymatic decarboxylation of histidine, which plays a pivotal role in a number of processes, including inflammation, allergic reactions, gastric acid secretion and neurotransmission [36]. Histamine was reported to inhibit production of reactive oxygen species (ROS) in CML cells via the H 2 -receptor (H 2 R) [37].…”

Section: Resultsmentioning

confidence: 99%

Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

Sun

Zhang

Yin

et al. 2014

IJMS

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Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of benzene-induced hematotoxicity. Liquid chromatography coupled with time of flight-mass spectrometry (LC-TOF-MS) and principal component analysis (PCA) was applied to investigate the variation of endogenous metabolites in bone marrow cells and plasma of male C3H/He mice. The mice were injected subcutaneously with benzene (0, 300, 600 mg/day) once daily for seven days. The body weights, relative organ weights, blood parameters and bone marrow smears were also analyzed. The results indicated that benzene caused disturbances in the metabolism of oxidation of fatty acids and essential amino acids (lysine, phenylalanine and tyrosine) in bone marrow cells. Moreover, fatty acid oxidation was also disturbed in plasma and thus might be a common disturbed metabolic pathway induced by benzene in multiple organs. This study aims to investigate the underlying molecular mechanisms involved in benzene hematotoxicity, especially in bone marrow cells.

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Section: Resultsmentioning

confidence: 99%

Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

Sun

Zhang

Yin

et al. 2014

IJMS

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“…GlyR α 3K RNA editing leads to proline-to-leucine substitution (P185L) in the ligand-binding domain and generates gain-of-function neurotransmitter receptors. 10 , 11 , 12 , 13 GlyR RNA editing is upregulated in the hippocampus of patients with TLE and leads to GlyR α 3K 185L -dependent tonic inhibition of neuronal excitability associated with neurodegeneration. 14 KCC2 expression promotes neuroprotection 14 , 15 but whether this involves regulation of transmembrane Cl − gradient or protein structural role is a matter of debate.…”

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confidence: 99%

Chloride transporter KCC2-dependent neuroprotection depends on the N-terminal protein domain

2015

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Neurodegeneration is a serious issue of neurodegenerative diseases including epilepsy. Downregulation of the chloride transporter KCC2 in the epileptic tissue may not only affect regulation of the polarity of GABAergic synaptic transmission but also neuronal survival. Here, we addressed the mechanisms of KCC2-dependent neuroprotection by assessing truncated and mutated KCC2 variants in different neurotoxicity models. The results identify a threonine- and tyrosine-phosphorylation-resistant KCC2 variant with increased chloride transport activity, but they also identify the KCC2 N-terminal domain (NTD) as the relevant minimal KCC2 protein domain that is sufficient for neuroprotection. As ectopic expression of the KCC2-NTD works independently of full-length KCC2-dependent regulation of Cl− transport or structural KCC2 C-terminus-dependent regulation of synaptogenesis, our study may pave the way for a selective neuroprotective therapeutic strategy that will be applicable to a wide range of neurodegenerative diseases.

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“…It is a pentameric ligand-gated ion channel, which is activated by γ-aminobutyric acid (GABA) and is modulated by various compounds. GABA A R modulators include benzodiazepines, barbiturates, propofol, ethanol, neurosteroids, cations (e.g., zinc ions), herbal components and odorants as well as the neurotransmitter histamine ( Bureau and Olsen, 1991 ; McDonald and Olsen, 1994 ; Thompson et al, 1996 ; Grobin et al, 1998 ; Hosie et al, 2003 ; Kim and McDonald, 2003 ; Belelli and Lambert, 2005 ; Li et al, 2006 ; Saras et al, 2008 ; Sergeeva et al, 2010 ; Rudolph and Knoflach, 2011 ; Kletke et al, 2013 ; Yip et al, 2013 ). Since 2008, it has been known that histamine could directly activate homomeric GABA A Rs composed of β subunits and modulate the heteromeric GABA A Rs α1β2 and α1β2γ2 ( Saras et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

“…In the brain histamine is released from the tuberomammillary nucleus which is involved in the wake-sleep regulation. Metabotropic histamine receptors (H 1 –H 4 ) mediate the physiological functions of histamine but at least three different types of neuronal ligand-gated ion channels are modulated by histamine ( Bekkers, 1993 ; Saras et al, 2008 ; Bianchi et al, 2011 ; Kletke et al, 2013 ). The possible mechanism of the modulation of GABA A Rs in the brain is still speculative ( Saras et al, 2008 ; Bianchi et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of amino acids involved in histamine potentiation of GABAA receptors

et al. 2015

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Histamine is a neurotransmitter involved in a number of physiological and neuronal functions. In mammals, such as humans, and rodents, the histaminergic neurons found in the tuberomamillary nucleus project widely throughout the central nervous system. Histamine acts as positive modulator of GABAA receptors (GABAARs) and, in high concentrations (10 mM), as negative modulator of the strychnine-sensitive glycine receptor. However, the exact molecular mechanisms by which histamine acts on GABAARs are unknown. In our study, we aimed to identify amino acids potentially involved in the modulatory effect of histamine on GABAARs. We expressed GABAARs with 12 different point mutations in Xenopus laevis oocytes and characterized the effect of histamine on GABA-induced currents using the two-electrode voltage clamp technique. Our data demonstrate that the amino acid residues β2(N265) and β2(M286), which are important for modulation by propofol, are not involved in the action of histamine. However, we found that histamine modulation is dependent on the amino acid residues α1(R120), β2(Y157), β2(D163), β3(V175), and β3(Q185). We showed that the amino acid residues β2(Y157) and β3(Q185) mediate the positive modulatory effect of histamine on GABA-induced currents, whereas α1(R120) and β2(D163) form a potential histamine interaction site in GABAARs.

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New insights in endogenous modulation of ligand-gated ion channels: Histamine is an inverse agonist at strychnine sensitive glycine receptors

Cited by 11 publications

References 38 publications

Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

Chloride transporter KCC2-dependent neuroprotection depends on the N-terminal protein domain

Identification of amino acids involved in histamine potentiation of GABAA receptors

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