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

Eur J Neurosci. 2000 Apr;12(4):1310-8. doi: 10.1046/j.1460-9568.2000.00023.x.

Abstract

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 microM) induced an increase in translocation to 124.6 +/- 5.7% of basal unstimulated conditions of the Ca++-independent protein kinase Cepsilon, but not of the Ca++-dependent isozyme beta. This effect was counteracted by 1-aminoindan-1,5-dicarboxylic acid (100 microM), an antagonist of metabotropic glutamate receptor 1. On the other hand, (+)-alpha-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 Cepsilon of 164 +/- 17.7% of basal unstimulated conditions. Because the (+)-MCPG induction of protein kinase Cepsilon 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 Cepsilon 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 Cepsilon translocation, and that (iii) a metabotropic glutamate receptor associated to phospholipase D might influence translocation of protein kinase C in a calcium-independent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / pharmacology*
  • Cerebral Cortex / cytology
  • Chelating Agents / pharmacology
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Cyclopropanes / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Enzyme Activation / drug effects
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Isoenzymes / metabolism*
  • Male
  • Neurons / chemistry
  • Neurons / enzymology
  • Neuroprotective Agents / pharmacology
  • Phospholipase D / metabolism*
  • Presynaptic Terminals / chemistry
  • Presynaptic Terminals / enzymology
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Protein Kinase C-epsilon
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Synaptosomes / enzymology*

Substances

  • 2-(2'-carboxy-3'-phenylcyclopropyl)glycine
  • Benzoates
  • Chelating Agents
  • Cyclopropanes
  • Excitatory Amino Acid Antagonists
  • Isoenzymes
  • Neuroprotective Agents
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • alpha-methyl-4-carboxyphenylglycine
  • Egtazic Acid
  • Prkce protein, rat
  • Protein Kinase C
  • Protein Kinase C beta
  • Protein Kinase C-epsilon
  • Phospholipase D
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Glycine