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.
(+)-MCPG induces PKCε translocation in cortical synaptosomes through a PLD-coupled mGluR / L. Pastorino, F. Colciaghi, F. Gardoni, S. Albani-Torregrossa, D.E. Pellegrini-Giampietro, F. Moroni, P.N.E. De Graan, F. Cattabeni, M.M.G. Di Luca. - In: EUROPEAN JOURNAL OF NEUROSCIENCE. - ISSN 0953-816X. - 12:4(2000), pp. 1310-1318.
|Titolo:||(+)-MCPG induces PKCε translocation in cortical synaptosomes through a PLD-coupled mGluR|
COLCIAGHI, FRANCESCA (Secondo)
CATTABENI, FLAMINIO NICOLA (Penultimo)
DILUCA, MONICA MARIA GRAZIA (Ultimo)
|Parole Chiave:||Cortex; Nerve terminal; Rat; Signal transduction|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2000|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1046/j.1460-9568.2000.00023.x|
|Appare nelle tipologie:||01 - Articolo su periodico|