GLUTAMATE ACTIVATES PHOSPHOLIPASE-D IN HIPPOCAMPAL SLICES OF NEWBORN AND ADULT-RATS

Phospholipase D (PLD) is activated by many neurotransmitters in a nove l signal transduction pathway. In the present work, PLD activity was s tudied comparatively in hippocampal slices of newborn and adult rats. Basal PLD activity in adult rats was almost three times higher than in newborn rats. In newborn rats, L-glutamate and 1S,3R-1-aminocyclopent ane-1,3-dicarboxylic acid (1S,3R-ACPD) time- and concentration-depende ntly enhanced the formation of [H-3]phosphatidylpropanol ([H-3]PP) and of [3H]phosphatidic acid in the presence of 2% propanol. N-Methyl-D-a spartate and kainate (both 1 mM) caused small, but significant increas es (approximately 50%), whereas pha-amino-3-hydroxy-5-methylisoxazole- 4-propionate (100 muM) was ineffective. Maximally effective concentrat ions of glutamate (1 mM) and of 1S,3R-ACPD (300 muM) increased the PLD activity to almost 300% of basal activity; the EC50 values were 199 a nd 47 muM, respectively. Glutamate receptor antagonists, such as DL-2- amino-3-phosphonopropionic acid (AP3), DL-2-amino-5-phosphonovaleric a cid, and kynurenate (all 1 mM) did not inhibit the glutamate-evoked in crease of PP formation. In slices of adult rats, the response to 1S,3R -ACPD was significant, but small, whereas glutamate was effective only in the presence of the glutamate uptake inhibitor L-aspartate-beta-hy droxamate. It is concluded that glutamate activates PLD in rat hippoca mpus through an AP3-resistant metabotropic receptor. This effect is su bject to ontogenetic development, with one important factor being glut amate uptake.