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

• Published in: The European journal of neuroscience Vol. 12; no. 4; pp. 1310 - 1318
• Main Authors: Pastorino, L., Colciaghi, F., Gardoni, F., Albani-Torregrossa, S., Pellegrini-Giampietro, D. E., Moroni, F., De Graan, P. N. E., Cattabeni, F., Di Luca, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-04-2000
• Subjects: cortex; nerve terminal; rat; signal transduction
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.1460-9568.2000.00023.x

We have tested whether different agonists of metabotropic glutamate receptors could induce translocation of selective protein kinase C isozymes in nerve terminals. In rat cortical synaptosomes 1S,3R‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD; 100 μm) induced an increase in translocation to 124.6 ± 5.7% of basal unstimulated conditions of the Ca++‐independent protein kinase Cε, but not of the Ca++‐dependent isozyme β. This effect was counteracted by 1‐aminoindan‐1,5‐dicarboxylic acid (100 μm), an antagonist of metabotropic glutamate receptor 1. On the other hand, (+)‐α‐methyl‐4‐carboxyphenylglycine [(+)‐MCPG], an antagonist of metabotropic glutamate receptors group I and II, did not antagonize the effect of 1S,3R‐ACPD, and per se induced a translocation of protein kinase Cε of 164 ± 17.7% of basal unstimulated conditions. Because the (+)‐MCPG induction of protein kinase Cε translocation was not antagonized by 1‐aminoindan‐1,5‐dicarboxylic acid, it is suggested that 1S,3R‐ACPD and (+)‐MCPG activate this signal transduction pathway through distinct membrane receptors. Indeed (2‐[2′′‐carboxy‐3′‐phenylcyclopropyl]glycine)‐13 (300 nm), a new compound known to antagonize metabotropic glutamate receptors coupled to phospholipase D, was able to antagonize protein kinase Cε translocation induced by (+)‐MCPG. Moreover (+)‐MCPG directly induced phospholipase D activity, measured as [3H]phosphoethanol production in cortical synaptosomes. These data suggest that in cortical nerve terminals (i) distinct metabotropic glutamate receptors, coupled to different signal transduction pathways, are present, (ii) (+)‐MCPG is able to induce protein kinase Cε translocation, and that (iii) a metabotropic glutamate receptor associated to phospholipase D might influence translocation of protein kinase C in a calcium‐independent manner.