Quantitative studies on some antagonists of N‐methyl D‐aspartate in slices of rat cerebral cortex

Harrison, Neil L.; Simmonds, M.A.

doi:10.1111/j.1476-5381.1985.tb12922.x

Cited by 467 publications

(263 citation statements)

References 21 publications

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“…In the early 1980's Lodge described ketamine as a selective inhibitor of NMDA receptor activity and neuronal nicotinic receptors (nAChRs) on Renshaw cells of the cat spinal cord (Anis et al, 1983). Ketamine is also an antagonist of NMDA receptors in rat cortex (Harrison & Simmonds, 1985) and blocks these receptors at sub-clinical concentrations, by acting both as a use-dependent open channel blocker (Honey et al, 1985) and through allosteric inhibition (Orser et al, 1997). Ketamine inhibits the response to acetylcholine or nicotine in both muscle and neuronal type nAChRs (Sumikawa et al, 1983;Wachtel & Wegrzynowicz, 1992;Scheller et al, 1996;Durieux, 1995;Furuya et al, 1999;Flood & Krasowski, 2000;Friederich et al, 2000;Sasaki et al, 2000;Yamakura et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant α7 and α4β2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes

Coates

Flood

2001

British J Pharmacology

104

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1 Ketamine is a dissociative anaesthetic that is formulated as Ketalar, which contains the preservative benzethonium chloride (BCl). We have studied the e ects of pure racemic ketamine, the preservative BCl and the Ketalar mixture on human neuronal nicotinic acetylcholine receptors (nAChRs) composed of the a7 subunit or a4 and b2 subunits expressed in Xenopus laevis oocytes. 2 Ketamine inhibited responses to 1 mM acetylcholine (ACh) in both the human a7 and a4b2 nAChRs, with IC 50 values of 20 and 50 mM respectively. Inhibition of the a7 nAChRs occurred within a clinically relevant concentration range, while inhibition of the a4b2 nAChR was observed only at higher concentrations. The Ketalar formulation inhibited nAChR function more e ectively than was expected given its ketamine concentration. The surprising increased inhibitory potency of Ketalar compared with pure ketamine appeared to be due to the activity of BCl, which inhibited both a7 (IC 50 value of 122 nM) and a4b2 (IC 50 value of 49 nM) nAChRs at concentrations present in the clinical formulation of Ketalar. 3 Ketamine is a noncompetitive inhibitor at both the a7 and a4b2 nAChR. In contrast, BCl causes a parallel shift in the ACh dose-response curve at the a7 nAChR suggesting competitive inhibition. Ketamine causes both voltage-dependent and use-dependent inhibition, only in the a4b2 nAChR. 4 Since a7 nAChRs are likely to be inhibited during clinical use of Ketalar, the actions of ketamine and BCl on this receptor subtype may play a role in the profound analgesia, amnesia, immobility and/or autonomic modulation produced by this anaesthetic. British Journal of Pharmacology (2001) 134, 871 ± 879 Keywords: Neuronal nicotinic acetylcholine receptors; benzethonium chloride; ketamine; anaesthetic mechanism Abbreviations: BCl, benzethonium chloride; nAChRs, neuronal nicotinic acetylcholine receptors IntroductionKetamine is a dissociative anaesthetic, that is an e ective analgesic, amnestic and hypnotic, but causes hallucinations that limit its usefulness as a clinical anaesthetic agent. Due to its potency as an analgesic and its sympathomimetic properties, ketamine ®nds extensive use in the treatment of burn patients in intensive care settings. In the early 1980's Lodge described ketamine as a selective inhibitor of NMDA receptor activity and neuronal nicotinic receptors (nAChRs) on Renshaw cells of the cat spinal cord (Anis et al., 1983). Ketamine is also an antagonist of NMDA receptors in rat cortex (Harrison & Simmonds, 1985) and blocks these receptors at sub-clinical concentrations, by acting both as a use-dependent open channel blocker (Honey et al., 1985) and through allosteric inhibition (Orser et al., 1997). Ketamine inhibits the response to acetylcholine or nicotine in both muscle and neuronal type nAChRs (Sumikawa et al., 1983;Wachtel & Wegrzynowicz, 1992;Scheller et al., 1996;Durieux, 1995;Furuya et al., 1999;Flood & Krasowski, 2000;Friederich et al., 2000;Sasaki et al., 2000;Yamakura et al., 2000). In the case of nAChRs containing the a4 subunit, ...

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Section: Introductionmentioning

confidence: 99%

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant α7 and α4β2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes

Coates

Flood

2001

British J Pharmacology

104

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“…To prepare of cortical slices is according to the mothod of Harrison and Simmonds (1985;Kim and Han, 2005). "Wedges" of rat cerebral cortex were prepared from the brains of male Wistar rats (200 g).…”

Section: Preparation Of Brain Slicesmentioning

confidence: 99%

Neuroprotective Effect of Taurine against Oxidative Stress-Induced Damages in Neuronal Cells

Yeon¹,

Kim²

2010

Biomolecules and Therapeutics

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-Taurine, 2-aminoethanesulfonic acid, is an abundant free amino acid present in brain cells and exerts many important biological functions such as anti-convulsant, modulation of neuronal excitability, regulation of learning and memory, anti-aggressiveness and anti-alcoholic effects. In the present study, we investigated to explore whether taurine has any protective actions against oxidative stress-induced damages in neuronal cells. ERK I/II regulates signaling pathways involved in nitric oxide (NO) and reactive oxygen species (ROS) production and plays a role in the regulation of cell growth, and apoptosis. We have found that taurine significantly inhibited AMPA induced cortical depolarization in the Grease Gap assays using rat cortical slices. Taurine also inhibited AMPA-induced neuronal cell damage in MTT assays in the differentiated SH-SY5Y cells. When the neuronal cells were treated with H 2 O 2 , levels of NO were increased; however, taurine pretreatment decreased the NO production induced by H2O2 to approximately normal levels. Interestingly, taurine treatment stimulated ERK I/II activity in the presence of AMPA or H2O2, suggesting the potential role of ERK I/II in the neuroprotection of taurine. Taken together, taurine has significant neuroprotective actions against AMPA or H2O2 induced damages in neuronal cells, possibly via activation of ERK I/II.

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“…The cortical wedge preparation described by Harrison and Simmonds (Harrison & Simmonds, 1985) and modi®ed by Burton et al (Burton et al, 1988) was used as previously described (CarlaÁ & Moroni, 1992). Brie¯y, wedges obtained from white swiss mice (male 15/25 g) were placed in a twocompartment bath and silicone grease was placed between the two portions of the bath.…”

Section: Preparation Of Cortical Wedgesmentioning

confidence: 99%

“…In pursuing this goal, we attempted to correlate, in rats, brain oxindole concentration with overall behaviour, and we studied oxindole e ects on: (i) the electrically evoked synaptic potentials and cell excitability in the CA1 region of rat hippocampal slices using both extracellular and intracellular recordings and (ii) the responses to ionotrophic glutamate receptor agonists in cortical wedge preparations (Harrison & Simmonds, 1985).…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological studies on oxindole, a neurodepressant tryptophan metabolite

Mannaioni

Carpenedo

Pugliese

et al. 1998

British J Pharmacology

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1 The aim of the present work was to investigate the electrophysiological e ects of oxindole, a tryptophan metabolite present in rat blood and brain, and recently proposed as a contributing factor in the pathogenesis of hepatic encephalopathy. 2 Using rat hippocampal slices in vitro and extra-or intracellular recordings, we evaluated oxindole e ects on the neurotransmission of the CA1 region following orthodromic stimulation of the Scha er collaterals. 3 Oxindole (0.3 ± 3 mM) decreased the amplitude of population spikes extracellularly recorded at the somatic level and of the fEPSPs recorded at the dendritic level. In intracellular recordings, oxindole (0.1 ± 3 mM) did not a ect the resting membrane potential or the neuronal input resistance, but reduced the probability of ®ring action potentials upon either synaptic or direct activation of the pyramidal cells. 4 Oxindole (0.3 ± 3 mM) increased the threshold and the latency of ®ring action potentials elicited by depolarizing steps without changing the duration or the peak amplitude of the spikes. It also signi®cantly increased the spike frequency adaptation induced by long lasting (400 ms) depolarizing stimuli. 5 In separate experiments, performed by measuring AMPA or NMDA-induced responses in cortical slices, oxindole (1 ± 3 mM) did not modify glutamate receptor agonist responses. 6 Our results show that concentrations of oxindole which may be reached in pathological conditions, signi®cantly decrease neuronal excitability by modifying the threshold of action potential generation.

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Quantitative studies on some antagonists of N‐methyl D‐aspartate in slices of rat cerebral cortex

Cited by 467 publications

References 21 publications

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant α7 and α4β2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant α7 and α4β2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes

Neuroprotective Effect of Taurine against Oxidative Stress-Induced Damages in Neuronal Cells

Electrophysiological studies on oxindole, a neurodepressant tryptophan metabolite

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