title: Synergistic effects of acetylcholine and glutamate on the release of arachidonic acid from cultured striatal neurons.
abstract: The activation of muscarinic and NMDA receptors by carbachol and NMDA, respectively, stimulated the release of [3H]arachidonic acid ([3H]AA) from cultured striatal neurons. Striking synergistic effects were observed when both agonists were coapplied. This synergistic response was suppressed by atropine or (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im ine hydrogen maleate and inhibited by magnesium. It was markedly reduced in the absence of external calcium and suppressed by mepacrine. NMDA strongly elevated the intracellular calcium concentration ([Ca2+]i), but carbachol was ineffective. Ionomycin, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate, or potassium depolarization, which increased [Ca2+]i but was ineffective on [3H]AA release, also potentiated the carbachol response. Sphingosine and Ro 31-8220 suppressed the responses evoked by carbachol, NMDA, or both agonists. However, no synergistic responses could be observed when phorbol 12-myristate 13-acetate was associated with either carbachol or NMDA. Together, these results suggest that both the massive influx of calcium induced by NMDA and the coupling of muscarinic receptors with a putative phospholipase A2 are required for the strong synergistic effects of carbachol and NMDA on [3H]AA release. Synergistic effects were also observed with acetylcholine and glutamate in the presence of magnesium, further revealing the physiological relevance of this process.
authors.affiliation: Chaire de Neuropharmacologie, INSERM U114, Collège de France, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Tencé
authors.forename: N
authors.initials: N
authors.lastname: Murphy
authors.forename: J
authors.initials: J
authors.lastname: Cordier
authors.forename: J
authors.initials: J
authors.lastname: Prémont
authors.forename: J
authors.initials: J
authors.lastname: Glowinski
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D004357:Drug Synergism; D018698:Glutamic Acid / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology
chemical_list: D016718:Arachidonic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D002217:Carbachol; D011493:Protein Kinase C; D000109:Acetylcholine; D002118:Calcium