A new type of glutamate receptor linked to inositol phospholipid metabolism

Sugiyama, Hiroyuki; Ito, Isao; Hirono, Chikara

doi:10.1038/325531a0

Cited by 702 publications

(282 citation statements)

References 20 publications

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“…Also, the observed high efficacy of QUIS as a rapid-acting neurotoxin is an unexplained finding appropriate for future investigation. QUIS neurotoxicity might, for example, be mediated by direct activation of inositol phospholipid metabolism and mobilization of intracellular calcium (Sugiyama et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists

1988

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The antagonist pharmacology of glutamate neurotoxicity was quantitatively examined in murine cortical cell cultures. Addition of 1- 3 mM DL-2-amino-5-phosphonovalerate (APV), or its active isomer D-APV, acutely to the exposure solution selectively blocked the neuroexcitation and neuronal cell selectively blocked the neuroexcitation and neuronal cell loss produced by N-methyl-D-aspartate (NMDA), with relatively little effect on that produced by either kainate or quisqualate. As expected, this selective NMDA receptor blockade only partially reduced the neuroexcitation or acute neuronal swelling produced by the broad-spectrum agonist glutamate; surprisingly, however, this blockade was sufficient to reduce glutamate- induced neuronal cell loss markedly. Lower concentrations of APV or D- APV had much less protective effect, suggesting that the blockade of a large number of NMDA receptors was required to acutely antagonize glutamate neurotoxicity. This requirement may be caused by the amplification of small amounts of acute glutamate-induced injury by subsequent release of endogenous NMDA agonists from injured neurons, as the “late” addition of 10–1000 microM APV or D-APV (after termination of glutamate exposure) also reduced resultant neuronal damage. If APV or D-APV were present both during and after glutamate exposure, a summation dose-protection relationship was obtained, showing substantial protective efficacy at low micromolar antagonist concentrations. Screening of several other excitatory amino acid antagonists confirmed that the ability to antagonize glutamate neurotoxicity might correlate with ability to block NMDA-induced neuroexcitation: The reported NMDA antagonists ketamine and DL-2-amino- 7-phosphono-heptanoate, as well as the broad-spectrum antagonist kynurenate, were all found to attenuate glutamate neurotoxicity substantially; whereas gamma-D-glutamylaminomethyl sulfonate and L- glutamate diethyl ester, compounds reported to block predominantly quisqualate or kainate receptors, did not affect glutamate neurotoxicity. The present study suggests that glutamate neurotoxicity may be predominantly mediated by the activation of the NMDA subclass of glutamate receptors--occurring both directly, during exposure to exogenous compound, and indirectly, due to the subsequent release of endogenous NMDA agonists. Given other studies linking NMDA receptors to channels with unusually high calcium permeability, this suggestion is consistent with previous data showing that glutamate neurotoxicity depends heavily on extracellular calcium.

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Section: Discussionmentioning

confidence: 99%

Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists

1988

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“…[Key words: calcium currents, intracellular calcium transients, glutamate, hippocampus] L-Glutamate is the major excitatory neurotransmitter in mammalian nervous system, which induces Ca, elevations directly through ionotropic (Hollmann et al, 1989;Boulter et al, 1990;Keinanen et al, 1990;Sommer et al, 1990) and metabotropic receptors (Sugiyama et al, 1987;Schoepp et al, 1990), and indirectly, through membrane depolarization that activates voltage-gated Ca channels (Kudo and Ogura, 1986;MacDermott et al, 1986;Murphy et al, 1987;Murphy and Miller, 1988). Vigorous Ca, elevations can be also induced in nerve cells by membrane depolarization alone (Kudo and Ogura, 1986;Murphy and Miller, 1988).…”

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confidence: 99%

Enhancement of voltage-gated Ca2+ currents induced by daily stimulation of hippocampal neurons with glutamate

1994

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The regulation of calcium channel currents (ICa) induced by daily stimulation (1 hr) with 10 microM glutamate was studied in full differentiated hippocampal cells in culture. We report a specific enhancement of the high-voltage-activated current type (HVA ICa) ongoing over days. The density of HVA ICa increased about twofold after the second glutamate session, and this enhancement was still observed after the fifth day of treatment, while low-voltage-activated calcium currents (LVA ICa) remained unchanged. During glutamate application, a transient increase of intracellular calcium (Cai) was observed, followed by a slow decay within 2–3 min, and substantial recovery in about 10 min. Similarly, Cai transients induced by periodic membrane depolarization mimicked the long-term effect of glutamate on ICa. These results demonstrate for the first time an increase of ICa in a time frame of days. Since the effect of glutamate on ICa was prevented by cycloheximide, neosynthesis of channel proteins presumably supports this enhancement.

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“…The entire 5.5 kb sBimR cDNA was labeled monitor the increase in the intracellular Ca 2+ concentration with s2p by random priming and used as a probe. ([Ca2+]i) caused by an activation of G-protein coupled recepPreparation of frozen sections of the salmon brain and hybridizators [3]. Using this system for screening, the first cDNA clone tion at high stringency were performed as described previously [16].…”

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Cloning and characterization of a bifunctional metabotropic receptor activated by both extracellular calcium and glutamate

Kubokawa¹,

Miyashita²,

Nagasawa³

et al. 1996

FEBS Letters

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A cDNA from salmon brain which induces a expression cloning and found to belong to the G-protein consistent activation of Ca 2+ dependent Cl-(Ca2+-Cl -) current coupled receptor family [10]. By the sequence homology, in Xenopus oocytes in the saline solution was isolated by an members of the CaR family were isolated from the kidney expression cloning method. The primary structure showed a high [11] and also from the brain [12]. The structural similarity homology with the metabotropic glutamate receptors (mGluR), of CaR and mGluR, especially mGluR1, has already been and a limited homology with the Ca2+/polyvalent cation noticed by some investigators [9][10][11][12][13]. The characteristic leareceptors (CAR). The encoded protein was functionally charture these two receptor families have in common is the pres-acterized for the sensitivity to extracellular Ca (Ca o ), and the ence of a long N-terminal cytoplasmic chain. However, it is consistent activation of Ca2+-CI -current was determined to be not yet known whether mGluR actually functions as a Ca 2÷ due to Ca 2+ contained in the saline solution. It was also receptor or not. confirmed that the encoded protein has a function to senseWe constructed a eDNA library from salmon brain with a glutamate. An increase in inositol 1,4,5-triphosphate turnover was observed when either Ca 2+ or glutamate was applied. Thus, view to isolating a G-protein coupled hormonal receptor by the encoded protein was identified as a bifunctional metabotropic expression cloning [14]. In the course of the electrophysiologreceptor for both Ca 2+ and glutamate. In addition, rat mGluRl~ ical screening, we happened to notice that a pool of the Ca o. This is the first report of eDNA library induced an increase in the basal level of the was also shown to be activated by 2+ a G-protein coupled receptor which is activated by two totallyCa2+-C1 -current without applying any agonist, and isolated different physiological agonists, the causative cDNA clone (eDNA for sBimR). The basal activity was found to be due to the activation of sBimR by Key words." Bifunctional; Metabotropic; Receptor; Calcium; Ca 2+ contained in the bath solution. The primary structure Glutamate; eDNA; Cloning exhibited a high degree of homology with mGluRla [4], and was characterized to be activated by glutamate.

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A new type of glutamate receptor linked to inositol phospholipid metabolism

Cited by 702 publications

References 20 publications

Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists

Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists

Enhancement of voltage-gated Ca2+ currents induced by daily stimulation of hippocampal neurons with glutamate

Cloning and characterization of a bifunctional metabotropic receptor activated by both extracellular calcium and glutamate

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