(+)-MCPG induces PKC epsilon translocation in cortical synaptosomes through a PLD-coupled mGluR

We have tested whether different agonists of metabotropic glutamate recepto rs could induce translocation of selective protein kinase C isozymes in ner ve terminals. In rat cortical synaptosomes 1S,3R-1-aminocyclopentane-1,3-di carboxylic acid (1S,3R-ACPD; 100 mu M) induced an increase in translocation to 124.6 +/- 5.7% of basal unstimulated conditions of the Ca++-independent protein kinase C epsilon, but not of the Ca++-dependent isozyme beta. This effect was counteracted by 1-aminoindan-1,5-dicarboxylic acid (100 mu M), an antagonist of metabotropic glutamate receptor 1. On the other hand, (+)- alpha-methyl-4-carboxyphenylglycine [(+)-MCPG], an antagonist of metabotrop ic glutamate receptors group I and II, did not antagonize the effect of 1S, 3R-ACPD, and per se induced a translocation of protein kinase C epsilon Of 164 +/- 17.7% Of basal unstimulated conditions. Because the (+)-MCPG induct ion of protein kinase C epsilon translocation was not antagonized by 1-amin oindan-1,5-dicarboxylic acid, it is suggested that 1S,3R-ACPD and (+)-MCPG activate this signal transduction pathway through distinct membrane recepto rs. Indeed (2-12"-carboxy-3'-phenylcyclopropylglycine )-13 (300 nM), a new compound known to antagonize metabotropic glutamate receptors coupled to ph ospholipase D, was able to antagonize protein kinase C epsilon translocatio n induced by (+)-MCPG. Moreover (+)-MCPG directly induced phospholipase D a ctivity, measured as [H-3]phosphoethanol production in cortical synaptosome s. These data suggest that in cortical nerve terminals (i) distinct metabot ropic glutamate receptors, coupled to different signal transduction pathway s, are present, (ii) (+)-MCPG is able to induce protein kinase C epsilon tr anslocation, and that (iii) a metabotropic glutamate receptor associated to phospholipase D might influence translocation of protein kinase C in a cal cium-independent manner.