(S)-5-fluorowillardiine-mediated neurotoxicity in cultured murine cortical neurones occurs via AMPA and kainate receptors

European Journal of Pharmacology
J A LarmP M Beart

Abstract

We have examined the neurotoxic effects of kainate, (S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and the novel AMPA-receptor preferring agonist (S)-5-fluorowillardiine in murine cultured cortical neurones. Kainate induced > 90% cell death (EC50 65 microM) and (S)-AMPA only about 50% cell death (EC50 3.1 microM), both in a monophasic dose-dependent manner. (S)-5-Fluorowillardiine also killed > 90% of neurones, however, in a biphasic dose-dependent manner (EC50 0.70 and 170 microM). Additionally, the neurotoxic effects of (S)-AMPA and (S)-5-fluorowillardiine (high-affinity component) were attenuated by the AMPA receptor antagonists LY293558 ((3,S,4aR, 6R,8aR)-6[2h91 H-tetrazol-5-yl)ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinol ine- 3-carboxylic acid). A component of kainate and (S)-5-fluorowillardiine (low-affinity component) neurotoxicity was blocked by the low-affinity kainate receptor antagonist NS-102 (5-nitro-6,7,8,9-tetrahydrobenzo[g]indole-2,3-dione-3-oxime). We have shown that both kainate and (S)-AMPA can effect substantial cell death in cortical neurones and that the novel agonist (S)-5-fluorowillardiine exerts its excitotoxicity through both AMPA- and kainate-preferring receptors.

References

Nov 1, 1992·Journal of Neurobiology·D W Choi
Sep 13, 1991·Journal of Immunological Methods·N W RoehmA L Glasebrook
Mar 1, 1993·Journal of Neurochemistry·P C May, P M Robison
Sep 15, 1994·European Journal of Pharmacology·T A VerdoornE O Nielsen
Jan 1, 1994·Annual Review of Neuroscience·M Hollmann, S Heinemann
Aug 15, 1993·European Journal of Pharmacology·T H JohansenE O Nielsen

❮ Previous
Next ❯

Citations

Jul 31, 1998·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·S ReesR Harding
Sep 2, 2008·Biological & Pharmaceutical Bulletin·Yuan MaKi-Wan Oh
May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·D OffenO Bernard
Jan 22, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Abraham Cisneros-MejoradoCarlos Matute
Jun 10, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Abraham Cisneros-MejoradoCarlos Matute
Sep 1, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Oksana SirenkoCassiano Carromeu
Aug 28, 2020·International Journal of Molecular Sciences·Asier RuizElena Alberdi
Jun 3, 2021·Biomolecules·Igor A SchepetkinMark T Quinn
Jun 30, 2006·Neurobiology of Disease·Miroslav GottliebCarlos Matute

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.