Prostaglandin E2 deteriorates N-methyl-d-aspartate receptor-mediated cytotoxicity possibly by activating EP2 receptors in cultured cortical neurons
| Autor: | Takao Ohyashiki, Tsuneo Takadera |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Prostaglandins E
Synthetic Agonist medicine.medical_specialty medicine.drug_class Prostaglandin E2 receptor Apoptosis Biology Receptors N-Methyl-D-Aspartate Dinoprostone General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Fetus Pregnancy Internal medicine Cyclic AMP medicine Animals Receptors Prostaglandin E RNA Messenger Alprostadil General Pharmacology Toxicology and Pharmaceutics Prostaglandin E2 Receptor Cells Cultured Cerebral Cortex Neurons Forskolin Reverse Transcriptase Polymerase Chain Reaction Neurodegeneration Glutamate receptor General Medicine Receptors Prostaglandin E EP2 Subtype medicine.disease Rats Endocrinology chemistry NMDA receptor Female lipids (amino acids peptides and proteins) medicine.drug |
| Zdroj: | Life Sciences. 78:1878-1883 |
| ISSN: | 0024-3205 |
| Popis: | The activation of glutamate receptors, particularly N-methyl-D-aspartate (NMDA) receptors, initiates ischemic cascade in the early stages of cerebral ischemia. Postischemia, cerebral ischemia is also associated with an inflammatory reaction that contributes to tissue damage. The up-regulation of neuronal cyclooxygenase-2 (COX-2) and elevation of prostaglandin E2 (PGE2) have been reported to occur after cerebral ischemic insult. We therefore studied whether the COX-2 reaction product PGE2 affects glutamate receptor-mediated cell death in cultured rat cortical cells. PGE2 was found to augment NMDA-mediated cell death. The transcription of EP1, EP2, EP3 and EP4 PGE2 receptor genes was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR). EP1, EP2 and EP3 receptor genes were found in cortical cells. Butaprost (an EP2 agonist) markedly enhanced NMDA-mediated cell death, whereas 17-phenyl trinor-PGE2 (an EP1 agonist) and sulprostone (an EP3 agonist) had little effect. Both PGE2 and butaprost elevated cAMP intracellular levels in the cortical cells; moreover, forskolin, an activator of adenylate cyclase, enhanced NMDA-mediated cell death. These results suggest that PGE2, acting via EP2 receptors, aggravates excitotoxic neurodegeneration by a cAMP-dependent mechanism. |
| Databáze: | OpenAIRE |
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