Neuronal Ca2+ stores: activation and function

Simpson, Peter B.; Challiss, R. A. John; Nahorski, Stefan R.

doi:10.1016/0166-2236(95)93919-o

Cited by 276 publications

(198 citation statements)

References 58 publications

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“…stores (Simpson et al, 1995), which, if contributing significantly to neurotoxicity, could confound the present findings and account for the excess toxicity of glutamate over NMDA. To examine the role of mGluRs, experiments were repeated in the presence of a range of concentrations of diverse mGluR agonists and antagonists (Table 1).…”

Section: A Component Of Glutamate Neurotoxicity Additive To That Prodmentioning

confidence: 84%

Distinct Influx Pathways, Not Calcium Load, Determine Neuronal Vulnerability to Calcium Neurotoxicity

Sattler¹,

Charlton

Hafner

et al. 1998

Journal of Neurochemistry

246

192

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Many forms of neurodegeneration are ascribed to excessive cellular Ca 2~loading (Ca2~hypothesis). We examined quantitatively whether factors other than 1Ca 2l oading were determinants of excitotoxic neurode~'eneration. Cell survival, morphology, free intracellular Cas1 concentration ([Ca2~]), and 45Ca2~accumulation were measured in cultured cortical neurons loaded with known quantities of Ca2through distinct transmembrane pathways triggered by excitatory amino acids, cell membrane depolarization, or Ca2ĩonophores. Contrary to the Ca2h ypothesis, the relationships between Ca2~load and cell survival, free [Ca2~]~, and Ca2~-inducedmorphological alterations depended primarily on the route of Ca2~influx, not the Ca2~load. Notably, Ca2~loading via NMDA receptor channels was toxic, whereas identical Ca2~loads incurred through voltage-sensitive Ca2~channels were completely innocuous. Furthermore, accounting quantitatively for Ca2~loading via NMDA receptors uncovered a previously unreported component of L-glutamate neurotoxicity apparently not mediated by ionotropic or metabotropic glutamate receptors. lt was synergistic with toxicity attributable to glutamate-evoked Ca2~loading, and correlated with enhanced cellular ATP depletion. This previously unrecognized toxic action of glutamate constituted a chief excitotoxic mechanism under conditions producing submaximal Ca2~loading. We conclude that (a) Ca2~neurotoxicity is a function of the Ca2~infltlx pathway, not Ca2 load, and (b) glutamate toxicity may not be restricted to its actions on glutamate receptors.

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Section: A Component Of Glutamate Neurotoxicity Additive To That Prodmentioning

confidence: 84%

Distinct Influx Pathways, Not Calcium Load, Determine Neuronal Vulnerability to Calcium Neurotoxicity

Sattler¹,

Charlton

Hafner

et al. 1998

Journal of Neurochemistry

246

192

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“…Alternatively, it is possible that Ca2"-influx regulated by mechanisms downstream of PIC (e.g. capacitative Ca2"-entry caused by intracellular Ca2"-store depletion) may contribute, although the importance of such mechanisms in excitable tissues is uncertain (see Simpson et al, 1995), and such mechanisms may not fully explain the contrasting effects on agonist and antagonist mGluR interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Facilitation of agoniststimulated PIC activity may be caused by Ca2" mobilization from intracellular stores or Ca2+-entry via a multitude of influx pathways (Simpson et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Differences in agonist and antagonist activities for two indices of metabotropic glutamate receptor‐stimulated phosphoinositide turnover

Mistry

Challiss

1996

British J Pharmacology

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“…These results indicate that the CGRP found in the perfusate of endotoxin originates from mesenteric perivascular nerves of capsaicinsensitive sensory nerves. Ca21 is crucial as a mediator of effector function of neurones in excitation-secretion coupling (Simpson et al, 1995). The observation that endotoxininduced increase in CGRP release was largely dependent on extracellular Ca2+ fulfils a requisite for considering this event an active process of release (Table1).…”

Section: Resultsmentioning

confidence: 99%

Rapid nitric oxide‐ and prostaglandin‐dependent release of calcitonin gene‐related peptide (CGRP) triggered by endotoxin in rat mesenteric arterial bed

Wang¹,

Wu²,

Tang³

et al. 1996

British J Pharmacology

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1 Our objective was to determine whether endotoxin (ETX) could directly trigger the release of calcitonin gene-related peptide (CGRP) from perivascular sensory nerves in the isolated mesenteric arterial bed (MAB) of the rat and to determine whether nitric oxide (NO) and prostaglandins (PGs) are involved. 2 ETX caused time-and concentration-dependent release of CGRP, and as much as a 17 fold increase in CGRP levels in the perfusate at 10-15 min after the administration of ETX (50 ,ug ml-'). 3 CGRP-like immunoreactivity in the perfusate was shown to co-elute with synthetic rat CGRP by reverse-phase h.p.l.c. 4 Pretreatment of MAB with capsaicin or ruthenium red inhibited ETX-induced CGRP release by 90% and 71%, respectively. ETX-evoked CGRP release was decreased by 84% during Ca2"-free perfusion.5 The release of CGRP evoked by ETX was enhanced by L-arginine by 43% and inhibited by Nwnitro-L-arginine (L-NOARG) and methylene blue by 37% and 38%, respectively. L-Arginine reversed the effect of L-NOARG. 6 Indomethacin and ibuprofen also inhibited the ETX-induced CGRP release by 34% and 44%, respectively. No additive inhibition could be found when L-NOARG and indomethacin were concomitantly incubated. 7 The data suggest that ETX triggers the release of CGRP from capsaicin-sensitive sensory nerves innervating blood vessels. The ETX-induced CGRP release is dependent on extracellular Ca2" influx and involves a ruthenium red-sensitive mechanism. Both NO and PGs appear to be involved in the ETXinduced release of CGRP in the rat mesenteric arterial bed.

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Neuronal Ca2+ stores: activation and function

Cited by 276 publications

References 58 publications

Distinct Influx Pathways, Not Calcium Load, Determine Neuronal Vulnerability to Calcium Neurotoxicity

Distinct Influx Pathways, Not Calcium Load, Determine Neuronal Vulnerability to Calcium Neurotoxicity

Differences in agonist and antagonist activities for two indices of metabotropic glutamate receptor‐stimulated phosphoinositide turnover

Rapid nitric oxide‐ and prostaglandin‐dependent release of calcitonin gene‐related peptide (CGRP) triggered by endotoxin in rat mesenteric arterial bed

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