CARBACHOL-INDUCED HYDROLYSIS OF PHOSPHOLIPIDS IN HIPPOCAMPAL SLICES MAY BE MEDIATED IN PART BY SUBSEQUENT ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS

We observed that AP-3, an antagonist of metabotropic glutamate recepto rs, reduced carbachol-induced hydrolysis of phospholipids in hippocamp al slices. This inhibition could be explained in different ways, e.g.: 1) AP-3 acts also as antagonist of muscarinic receptors mediating the hydrolysis of phospholipids induced by carbachol, 2) Carbachol induce s the release of glutamate which, by activating metabotropic glutamate receptors, leads to additional hydrolysis of phospholipids. The aim o f this work was to test these possibilities. It is shown that AP-3 red uces carbachol-induced hydrolysis of phospholipids in hippocampal slic es but not in cerebellar neurons at 10-14 days of culture, when these cells are not able to induce hydrolysis of phospholipids following act ivation of metabotropic glutamate receptors. It is also shown that car bachol induces a release of [H-3]aspartate in hippocampal slices. The results reported suggest that the hydrolysis of phospholipids induced by carbachol in hippocampal slices would have two components. One part would be due to direct activation by carbachol of muscarinic receptor s associated to activation of phospholipase C. This part would not be inhibited by AP-3. The second part would be due to subsequent release of glutamate and activation of metabotropic glutamate receptors. This part would be inhibited by AP-3.