Regulation of N-Methyl-d-aspartate receptor-mediated calcium transport and norepinephrine release in rat hippocampus synaptosomes by polyamines |
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Authors: | Farida Siddiqui Zafar Iqbal |
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Affiliation: | (1) Department of Neurology, Northwestern University Medical School, 303 E. Chicago Avenue, Mail Code T-235, 60611-3008 Chicago, Illinois;(2) Institute for Neuroscience, Northwestern University Medical School, 303 E. Chicago Avenue, Mail Code T-235, 60611-3008 Chicago, Illinois;(3) Markey Center for Developmental Biology, Northwestern University Medical School, 60611-3008 Chicago, Illinois;(4) Neurology Research Service, Department of Veterans, Affairs Lakeside Medical Center, 60611-3008 Chicago, Illinois |
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Abstract: | The role of polyamines (PA) synthesis in NMDA receptor-mediated45Ca2+ fluxes and norepinephrine release was studied in rat hippocampal synaptosomes. NMDA (50M) caused a sharp (>2-fold) transient increase in PA synthesis regulating enzyme, ornithine decarboxylase (ODC) activity with concomitant elevation in PA levels in the order putrescine>spermidine>spermine. ODC inhibitor, -difluoromethylornithine (DFMO), and NMDA antagonist, 2-amino-5-phosphonovaleric acid (D-AP5), both blocked increases in ODC activity and PA levels. Activation of NMDA receptors induced a sharp (3 to 4-fold) and quick (15 seconds) increase in45Ca2+ uptake by synaptosomes within 15 seconds of exposure at 37°C. The efflux of45Ca2+ and3H-norepinephrine (NE) release at 22°C from pre-loaded synaptosomes was also significantly (2 to 4-fold) enhanced by NMDA within 15 seconds. These NMDA receptor-mediated effects on calcium fluxes and NE release were blocked by NMDA receptor-antagonists (DAP-5 and MK-801) and PA synthesis inhibitor, DFMO and the DFMO inhibition nullified by exogenous putrescine. These observations establish that ODC/PA cascade play an important role in transduction of excitatory amino acid mediated signals at NMDA receptors.Special issue dedicated to Dr. Sidney Ochs. |
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Keywords: | D-AP5, 2-amino-5-phosphonovaleric acid DFMO, /content/q51143637492t2g3/xxlarge945.gif" alt=" agr" align=" BASELINE" BORDER=" 0" >-difluoromethylornithine EGTA, ethylene-bis-(oxyethelene nitrilo) tetra acetic acid Hepes, N-2-hydroxyethyl piperazine-N /content/q51143637492t2g3/xxlarge8242.gif" alt=" prime" align=" BASELINE" BORDER=" 0" >-2-ethane sulfonic acid NMDA, N-methyl-D-aspartate NE, Norepinephrine ODC, Ornithine decarboxylase PA, Polyamines PSS, Physiological saline solution Tris, Tris (hydoxymethyl)amino methane |
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