On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus

Brown, Ritchie E.; Haas, Helmut L.

doi:10.1111/j.1469-7793.1999.777ab.x

Cited by 112 publications

(80 citation statements)

References 34 publications

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“…The H 3 receptor acts as an autoreceptor regulating histamine synthesis and release (Arrang et al, 1983;Takeshita et al, 1998;Torrent et al, 2005), and through its heteroreceptor it may inhibit release of other neurotransmitters (e.g., glutamate and GABA) (Brown and Haas, 1999;Korotkova et al, 2002). In our study, thioperamide increased the neuroprotective effect of histaminergic neurons, whereas clobenpropit did not have any effect.…”

Section: Mechanisms Of Histamine-mediated Neuroprotective Effectmentioning

confidence: 47%

Histaminergic Neurons Protect the Developing Hippocampus from Kainic Acid-Induced Neuronal Damage in an Organotypic Coculture System

Kukko‐Lukjanov

Soini²,

Taira³

et al. 2006

J. Neurosci.

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The central histaminergic neuron system inhibits epileptic seizures, which is suggested to occur mainly through histamine 1 (H 1 ) and histamine 3 (H 3 ) receptors. However, the importance of histaminergic neurons in seizure-induced cell damage is poorly known. In this study, we used an organotypic coculture system and confocal microscopy to examine whether histaminergic neurons, which were verified by immunohistochemistry, have any protective effect on kainic acid (

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Section: Mechanisms Of Histamine-mediated Neuroprotective Effectmentioning

confidence: 47%

Histaminergic Neurons Protect the Developing Hippocampus from Kainic Acid-Induced Neuronal Damage in an Organotypic Coculture System

Kukko‐Lukjanov

Soini²,

Taira³

et al. 2006

J. Neurosci.

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“…We have also demonstrated that coassembly of Kv1.5 subunits confers sensitivity to Src-family PTK signaling upon Kv1.4-containing rapidly inactivating channels that carry transient potassium currents. Transient presynaptic potassium currents play an important role in controlling hippocampal action potential kinetics and consequent neurotransmitter release (26)(27)(28). Thus, the coassembly of Kv1.5 subunits into presynaptic Kv1.4-containing rapidly inactivating potassium channels in hippocampal neurons could couple modulation of action potential duration and neurotransmitter release to Srcfamily PTK activation.…”

Section: Discussionmentioning

confidence: 99%

A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors

Nitabach¹

2001

Proceedings of the National Academy of Sciences

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It is an open question how ion channel subunits that lack proteinprotein binding motifs become targeted and covalently modified by cellular signaling enzymes. Here, we show that Src-family protein tyrosine kinases (PTKs) bind to heteromultimeric Shakerfamily voltage-gated potassium (Kv) channels by interactions between the Src homology 3 (SH3) domain and the proline-rich SH3 domain ligand sequence in the Shaker-family subunit Kv1.5. Once bound to Kv1.5, Src-family PTKs phosphorylate adjacent subunits in the Kv channel heteromultimer that lack proline-rich SH3 domain ligand sequences. This SH3-dependent tyrosine phosphorylation contributes to significant suppression of voltage-evoked currents flowing through the heteromultimeric channel. These results demonstrate that Kv1.5 subunits function as SH3-dependent adaptor proteins that marshal Src-family kinases to heteromultimeric potassium channel signaling complexes, and thereby confer functional sensitivity upon coassembled channel subunits that are themselves not bound directly to Src-family kinases by allowing their phosphorylation. This is a mechanism for information transfer between subunits in heteromultimeric ion channels that is likely to underlie the generation of combinatorial signaling diversity in the control of cellular electrical excitability. P resent understanding of the interaction between regulatory signaling enzymes and ion channels is limited in several respects. First, although almost all ion channel subunits that have been tested are biophysically modulated in response to covalent modification by a variety of protein kinases (1-12), most ion channel subunits do not exhibit known protein-protein binding module ligand sequences. It is thus an open question how such ion channel subunits that lack protein-protein binding motifs become targeted by particular signaling enzymes. Second, although the majority of ion channels found in native tissues are heteromultimers (13-16), mechanistic analyses of ion channel interactions with signaling enzymes have been limited to homomultimers consisting of multiple copies of a single ion channel subunit. Thus, the functional regulation of heteromultimeric channels by signaling enzymes and the nature of the interaction between distinct subunits within a heteromultimer and stably associated signaling enzymes remains unexplored.It has been demonstrated that voltage-gated potassium (Kv)1.5-containing channels are associated with Src-family protein tyrosine kinases (PTKs) by means of Src homology 3 (SH3) domain interactions with the Kv1.5 proline-rich SH3 domain ligand sequence (ref. 1; T.C.H., J. Marquez, and I. B. Levitan, personal communication). When coexpressed in mammalian cells in culture, Kv1.5 is tyrosine phosphorylated by Src, and voltage-evoked currents are dramatically suppressed as a consequence (1). It is known that members of the mammalian Shaker family form heteromultimers in the mammalian brain (13,14,16). Whether heteromultimer formation provides a mechanism for the functionally relevant transfer of ...

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“…2a). This inverse relationship between the efficacy of LR* and the strength of the stimulus may therefore not only reflect the effect of calcium influx on stimulus-release coupling (30,34), as has been assumed so far (24), but also the competition of R* with LR* for G proteins, leading in the absence of R* (low stimulus) to a higher LR*͞G protein stoichiometry (i.e., higher inhibition of release; Figs. 2a and 3).…”

Section: Sleep-wake Cycle (In Vivo)mentioning

confidence: 99%

Protean agonism at histamine H ₃ receptors in vitro and in vivo

Gbahou

Rouleau

Morisset-Lopez

et al. 2003

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

132

103

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G protein-coupled receptors (GPCRs) are allosteric proteins that adopt inactive (R) and active (R*) conformations in equilibrium. R* is promoted by agonists or occurs spontaneously, leading to constitutive activity of the receptor. Conversely, inverse agonists promote R and decrease constitutive activity. The existence of another pharmacological entity, referred to as ''protean'' agonists (after Proteus, the Greek god who could change shape), was assumed on theoretical grounds. It was predicted from the existence of constitutive activity that a same ligand of this class could act either as an agonist or an inverse agonist at the same GPCR. Here, we show that proxyfan, a high-affinity histamine H 3-receptor ligand, acts as a protean agonist at recombinant H 3 receptors expressed in the same Chinese hamster ovary cells. In support of the physiological relevance of the process, we show that proxyfan also behaves as a protean agonist at native H 3 receptors known to display constitutive activity. On neurochemical and behavioral responses in rodents and cats, proxyfan displays a spectrum of activity ranging from full agonism to full inverse agonism. Thus, protean agonism demonstrates the existence of ligand-directed active states LR* different from, and competing with, constitutively active states R* of GPCRs, and defines a pharmacological entity with important therapeutic implications.

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On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus

Cited by 112 publications

References 34 publications

Histaminergic Neurons Protect the Developing Hippocampus from Kainic Acid-Induced Neuronal Damage in an Organotypic Coculture System

Histaminergic Neurons Protect the Developing Hippocampus from Kainic Acid-Induced Neuronal Damage in an Organotypic Coculture System

A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors

Protean agonism at histamine H ₃ receptors in vitro and in vivo

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On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus

Cited by 112 publications

References 34 publications

Histaminergic Neurons Protect the Developing Hippocampus from Kainic Acid-Induced Neuronal Damage in an Organotypic Coculture System

Histaminergic Neurons Protect the Developing Hippocampus from Kainic Acid-Induced Neuronal Damage in an Organotypic Coculture System

A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors

Protean agonism at histamine H 3 receptors in vitro and in vivo

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Protean agonism at histamine H ₃ receptors in vitro and in vivo