Synergistic effects of acetylcholine and glutamate on the release of arachidonic acid from cultured striatal neurons

• Published in: Journal of neurochemistry Vol. 64; no. 4; p. 1605
• Main Authors: Tencé, M, Murphy, N, Cordier, J, Prémont, J, Glowinski, J
• Format: Journal Article
• Language: English
• Published: England 01.04.1995
• Subjects: Acetylcholine - pharmacology; Animals; Arachidonic Acid - metabolism; Calcium - physiology; Carbachol - pharmacology; Cells, Cultured; Corpus Striatum - cytology; Corpus Striatum - metabolism; Drug Synergism; Glutamic Acid - pharmacology; Mice; Mice, Inbred Strains; N-Methylaspartate - pharmacology; Neurons - metabolism; Protein Kinase C - physiology
• ISSN: 0022-3042
• DOI: 10.1046/j.1471-4159.1995.64041605.x

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.