Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors

Kawabata, Sueo; Tsutsumi, Rie; Kohara, Atsuyuki; Yamaguchi, Tokio; Nakanishi, Shigetada; Okada, Masamichi

doi:10.1038/383089a0

Cited by 267 publications

(269 citation statements)

References 28 publications

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“…HEK 293 cells transfected with mGluR1a revealed, upon stimulation, fast transient [Ca 2+ ] i increases. Similar responses have been reported in HEK 293 cells expressing mGluR1a (Kawabata et al, 1996;Gomeza et al, 1996;Flor et al, 1996) and in CHO cells transfected with mGluR1b (Knopfel et al, 1995). In contrast, the analysis of Ca 2+ responses in HEK 293 cells expressing mGluR5a revealed [Ca 2+ ] i oscillations in almost all cells that were able to respond to agonists.…”

Section: Discussionsupporting

confidence: 82%

“…Untransfected HEK 293 and CHO cells do not express endogenous metabotropic or ionotropic glutamate receptors functionally coupled to PLC and intracellular Ca 2+ mobilization (Gabellini et al, 1994;Kawabata et al, 1996;Daggett et al, 1995). In transfected cells activation of mGluR1a and mGluR5a elicits different patterns of intracellular Ca 2+ responses suggesting that these two receptors play distinct roles in intracellular Ca 2+ homeostasis.…”

Section: Discussionmentioning

confidence: 99%

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Cyclothiazide selectively inhibits mGluR1 receptors interacting with a common allosteric site for non-competitive antagonists

et al. 2007

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Metabotropic glutamate receptors mGluR1 and mGluR5 stimulate phospholipase C, leading to an increased inositol triphosphate level and to Ca 2+ release from intracellular stores. Cyclothiazide (CTZ), known as a blocker of AMPA receptor desensitization, produced a non-competitive inhibition of [Ca 2+ ] i increases induced by mGluR agonists in HEK 293 cells transfected with rat mGluR1a but had no effect on the [Ca 2+ ] i signals in cells expressing rat mGluR5a. In cells expressing mGluR1, CTZ also inhibited phoshoinositide hydrolysis, as well as cAMP accumulation and arachidonic acid release induced by mGluR1 agonists, indicating a direct inhibition of the receptor and not of a particular signal transduction system. However, CTZ failed to antagonize cAMP inhibition stimulated by rat mGluR2, -3, -4, -6, -7 and -8 receptors confirming its selectivity for mGluR1. The use of chimeric receptors with substituted N-terminal domains showed that CTZ did not interact with the N-terminal mGluR1a domain. Instead, mutation analysis revealed that CTZ interacts with the Thr-815 and Ala-818 residues, located at the 7 th transmembrane domain, similarly as the mGluR1-selective antagonist CPCCOEt. In primary cultures of cerebellar granule neurons, expressing native metabotropic and ionotropic glutamate receptors, the final outcome of CTZ effects depended on its combined ability to potentiate AMPA receptors and inhibit mGluR1a receptors.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Cyclothiazide selectively inhibits mGluR1 receptors interacting with a common allosteric site for non-competitive antagonists

et al. 2007

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“…The rhythmic activity induced by mGluR activation in type I and type II interneurons, which is most likely mGluR1-mediated, is independent of the previously reported intracellular Ca 2ϩ oscillations, which were shown to be mGluR5-dependent (Kawabata et al, 1996). Hence, one would predict the absence of Ca 2ϩ oscillations in type II interneurons because they express mGluR1 only.…”

Section: Discussionmentioning

confidence: 70%

Differential Expression of Group I Metabotropic Glutamate Receptors in Functionally Distinct Hippocampal Interneurons

et al. 2000

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Metabotropic glutamate receptors (mGluRs) have been proposed to be involved in oscillatory rhythmic activity in the hippocampus. However, the subtypes of mGluRs involved and their precise distribution in different populations of interneurons is unclear. In this study, we combined functional analysis of mGluR-mediated inward currents in CA1 oriens-alveus interneurons with anatomical and immunocytochemical identification of these interneurons and expression analysis of group I mGluR using single-cell reverse transcription-PCR (RT-PCR). Four major interneuron subtypes could be distinguished based on the mGluR-mediated inward current induced by the application of 100 M trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) under voltage-clamp conditions and the action potential firing pattern under current-clamp conditions. Type I interneurons responded with a large inward current of ϳ224 pA, were positive for somatostatin, and the majority expressed both mGluR1 and mGluR5. Type II interneurons responded with an inward current of ϳ80 pA, contained calbindin, and expressed mainly mGluR1. Type III interneurons responded with an inward current of ϳ60 pA. These interneurons were fast-spiking, contained parvalbumin, and expressed mainly mGluR5. Type IV interneurons did not respond with an inward current upon application of ACPD, yet they expressed group I mGluRs. Activation of group I mGluRs under currentclamp conditions increased spike frequency and resulted in rhythmic firing activity in type I and II, but not in type III and IV, interneurons. RT-PCR results suggest that activation of mGluR1 in the subsets of GABAergic interneurons, classified here as type I and II, may play an important role in mediating synchronous activity.

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“…We have recently reported that mGluRl and mGluR5, although both coupling to the IP3/Ca 2~cas-cade, induce distinct [Ca2~] 1responses in the heterologous expression system (Kawabata et al, 1996). In both HEK293 and NIH3T3 cells, mGluRl shows a single-peaked, nonoscillatory [Ca 2~I~response to glutamate application, whereas mGluR5 evokes an oscillatory [Ca2~] 1 response by glutamate exposure.…”

mentioning

confidence: 99%

The Metabotropic Glutamate Receptor mGluR5 Induces Calcium Oscillations in Cultured Astrocytes via Protein Kinase C Phosphorylation

Nakahara

Okada²,

Nakanishi

1997

Journal of Neurochemistry

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133

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Abstract:The metabotropic glutamate receptor mGluR5, but not the closely related mGluRl, is expressed in cultured astrocytes, and this expression is up-regulated by specific growth factors. We investigated the capability and underlying mechanisms of mGluR5 to induce oscillatory responses of intracellular calcium concentration ([Ca 2~]) in cultured rat astrocytes. recordings indicated that an mGluR-selective agonist, (1 S,3R)-1 -aminocyclopentane-1,3-dicarboxylate (1 S,3R-ACPD), elicits [Ca2~], oscillations in good agreement with the growth factor-induced up-regulation of mGluR5 in cultured astrocytes. A protein kinase C (PKC) inhibitor, bisindolylmaleimide I, converted a 1S,3R-ACPD-mediated oscillatory response into a nonoscillatory response. In addition, the PKC activator phorbol 12-myristate 13-acetate completely abolished the [Ca2~]increase. These and other pharmacological properties of 1S,3R-ACPD-induced [Ca2~]õscillations correlate well with those of the cloned mGluR5 characterized in heterologous expression systems. Furthermore, the potential involvement of protein phosphatases in [Ca2~]õscilla-tions is suggested. The present study demonstrates that mGluR5 is capable of inducing [Ca2~] 1 oscillations in cultured astrocytes and that phosphorylation/dephosphorylation of mGluR5 is critical in [Ca 2~]oscillations, analogous to the cloned mGluR5 expressed in heterologous cell lines.

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Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors

Cited by 267 publications

References 28 publications

Cyclothiazide selectively inhibits mGluR1 receptors interacting with a common allosteric site for non-competitive antagonists

Cyclothiazide selectively inhibits mGluR1 receptors interacting with a common allosteric site for non-competitive antagonists

Differential Expression of Group I Metabotropic Glutamate Receptors in Functionally Distinct Hippocampal Interneurons

The Metabotropic Glutamate Receptor mGluR5 Induces Calcium Oscillations in Cultured Astrocytes via Protein Kinase C Phosphorylation

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