P2 receptor antagonist PPADS confers neuroprotection against glutamate/NMDA toxicity. 2005

Yanpeng Lin, and Angele Desbois, and Susan Jiang, and Sheng T Hou
Department of Clinical Neurological Sciences, The No 252 Hospital of P.L.A., 81 Huayuan Street, Baoding City 071000, Hebei Province, PR China.

The present study investigated the role of pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium salt (PPADS), a P2 receptor antagonist, in protecting mouse cerebellar granule neurons (CGNs) against glutamate/NMDA-induced neuronal death. Neurotoxicity caused by 50 microM glutamate or 200 microM NMDA was significantly reduced in CGNs treated with PPADS. Such neuroprotection was in a time- and dose-dependent manner. The possibility that PPADS may block glutamate/NMDA-mediated intracellular Ca2+ influx to CGNs was investigated using temperature-controlled platereader measurements of fluorescence intensity of CGNs loaded with Ca2+-sensitive fluorescent dye Fluo-4AM. Interestingly, the rapid increase of calcium influx following glutamate/NMDA treatment was not significantly affected by prior treatment with PPADS. In contrast, MK801, a specific NMDA receptor antagonist, completely blocked intracellular Ca2+ influx. Taken together, these data suggest that inhibition of the P2 receptor may directly modulate NMDA receptor-mediated neurotoxicity through a Ca2+-independent mechanism.

UI MeSH Term Description Entries
D011732 Pyridoxal Phosphate This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE). Pyridoxal 5-Phosphate,Pyridoxal-P,Phosphate, Pyridoxal,Pyridoxal 5 Phosphate,Pyridoxal P
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016202 N-Methylaspartate An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA). N-Methyl-D-aspartate,NMDA,N-Methyl-D-aspartic Acid,Acid, N-Methyl-D-aspartic,N Methyl D aspartate,N Methyl D aspartic Acid,N Methylaspartate
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D058919 Purinergic P2 Receptor Antagonists Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS. P2 Purinoceptor Antagonists,P2 Purinoceptor Blockers,Purinergic P2 Receptor Blockers,Antagonists, P2 Purinoceptor,Blockers, P2 Purinoceptor,Purinoceptor Antagonists, P2,Purinoceptor Blockers, P2
D018048 Receptors, Purinergic P2 A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system. ADP Receptors,ATP Receptors,P2 Purinoceptors,Purinergic P2 Receptors,Receptors, ADP,Receptors, ATP,ADP Receptor,ATP Receptor,P2 Purinoceptor,Receptor, Purinergic P2,P2 Receptor, Purinergic,P2 Receptors, Purinergic,Purinergic P2 Receptor,Purinoceptor, P2,Purinoceptors, P2,Receptor, ADP,Receptor, ATP
D018696 Neuroprotective Agents Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. Neuroprotectant,Neuroprotective Agent,Neuroprotective Drug,Neuroprotectants,Neuroprotective Drugs,Neuroprotective Effect,Neuroprotective Effects,Agent, Neuroprotective,Agents, Neuroprotective,Drug, Neuroprotective,Drugs, Neuroprotective,Effect, Neuroprotective,Effects, Neuroprotective
D018698 Glutamic Acid A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM. Aluminum L-Glutamate,Glutamate,Potassium Glutamate,D-Glutamate,Glutamic Acid, (D)-Isomer,L-Glutamate,L-Glutamic Acid,Aluminum L Glutamate,D Glutamate,Glutamate, Potassium,L Glutamate,L Glutamic Acid,L-Glutamate, Aluminum

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