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Metabotropic Glutamate Receptors in Cultured Cerebellar Granule Cells: Developmental Profile
Author(s) -
Aronica E.,
Condorelli D. F.,
Nicoletti F.,
Dell'Albani P.,
Amico C.,
Balázs R.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03185.x
Subject(s) - metabotropic glutamate receptor , metabotropic receptor , metabotropic glutamate receptor 1 , nmda receptor , glutamate receptor , biology , receptor , granule cell , biochemistry , medicine , endocrinology , microbiology and biotechnology , central nervous system , dentate gyrus
Excitatory amino acid (EAA)‐induced polyphosphoinositide (PPI) hydrolysis was studied during the development in culture of cerebellar granule cells. The developmental pattern was similar using metabotropic glutamate (Glu) receptor (mGluR) agonists, including L‐Glu, quisqualate, and trans ‐(±)‐1‐amino‐1,3‐cyclopentanedicarboxylic acid: The stimulation of [ 3 H]inositol monophosphate ([ 3 H]‐InsP) formation was low at 2 days in vitro (DIV), but the response increased steeply, reaching a peak at 4 DIV, followed by a progressive decline. In contrast, carbamylcholine‐induced PPI hydrolysis exhibited a plateau after a pronounced increase during the first week in vitro. At 6 DIV, but not at 4 DIV, when the activity peaked, PPI hydrolysis elicited by Glu was reduced by the N ‐methyl‐ d ‐aspartate (NMDA) receptor antagonist MK‐801, indicating that in cultured granule cells, NMDA receptors contribute to [ 3 H]‐InsP formation and that this component of the response develops relatively late. Accordingly, NMDA‐induced [ 3 H]‐InsP formation, estimated under Mg 2+ ‐free conditions, increased markedly from very low values at 2 DIV to a plateau at 8–10 DIV. The developmental pattern of EAA‐induced PPI hydrolysis was paralleled by changes in the level of an mRNA for a specific mGluR subtype ( mGluR1 mRNA). RNA blot analysis performed with the pmGR1 cDNA probe revealed that the hybridization signal in RNA extracts from cultures at 1 DIV was very weak, but mGluR mRNA levels increased dramatically between 1 and 3 DIV, followed by a progressive decrease, so that by 15 DIV the mRNA levels were only ∼10% of the values at 3 DIV. These observations indicate that the functional expression of the mGluR is subject to developmental regulation, which critically involves receptor mRNA levels.