REGULATION OF N-METHYL-D-ASPARTATE RECEPTOR-MEDIATED CALCIUM-TRANSPORT AND NOREPINEPHRINE RELEASE IN RAT HIPPOCAMPUS SYNAPTOSOMES BY POLYAMINES

The role of polyamines (PA) synthesis in NMDA receptor-mediated Ca-45( 2+) fluxes and norepinephrine release was studied in rat hippocampal s ynaptosomes. NMDA (50 mu M) caused a sharp (>2-fold) transient increas e in PA synthesis regulating enzyme, ornithine decarboxylase (ODC) act ivity with concomitant elevation in PA levels in the order putrescine > spermidine > spermine. ODC inhibitor, alpha-difluoromethylornithine (DFMO), and NMDA antagonist, 2-amino-5-phosphonovaleric acid (D-APS), both blocked increases in ODC activity and PA levels. Activation of NM DA receptors induced a sharp (3 to 4-fold) and quick (15 seconds) incr ease in Ca-45(2+) uptake by synaptosomes within 15 seconds of exposure at 37 degrees C. The efflux of Ca-45(2+) and H-3-norepinephrine (NE) release at 22 degrees C from pre-loaded synaptosomes was also signific antly (2 to 4-fold) enhanced by NMDA within 15 seconds. These NMDA rec eptor-mediated effects on calcium fluxes and NE release were blocked b y NMDA receptor-antagonists (DAP-5 and MK-801) and PA synthesis inhibi tor, DFMO and the DEMO inhibition nullified by exogenous putrescine. T hese observations establish that ODC/PA cascade play an important role in transduction of excitatory amino acid mediated signals at NMDA rec eptors.