Metabotropic glutamate receptors in cultured cerebellar granule cells: Developmental profile

E. Aronica, D. F. Condorelli, F. Nicoletti, P. Dell'Albani, C. Amico, R. Balázs

Research output: Contribution to journalArticle

Abstract

Excitatory amino acid (EAA)-induced polyphosphoinsitide (PPI) hydrolysis was studied during the development in culture of cerebellar granule cells. The developmental pattern was similar using metahotropic glutamate (Glu) receptor (mGluR) agonists, including L-Glu, quisqualate, and trans-(±)-1-amino-1,3-cyclopentanedicarboxylic acid: The stimulation of [3H]inositol monophosphate ([3H]-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 [3H]-InsP formation and that this component of the response develops relatively late. Accordingly. NMDA-induced [3H]-InsP formation, estimated under Mg2+-free conditions, in-creased 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 (mdGluRI 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.

Original languageEnglish
Pages (from-to)559-565
Number of pages7
JournalJournal of Neurochemistry
Volume60
Issue number2
Publication statusPublished - 1993

Keywords

  • Cerebellar granule cells
  • Development
  • Metabotropic glutamate receptors
  • mRNA
  • Phosphoinositide hydrolysis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Aronica, E., Condorelli, D. F., Nicoletti, F., Dell'Albani, P., Amico, C., & Balázs, R. (1993). Metabotropic glutamate receptors in cultured cerebellar granule cells: Developmental profile. Journal of Neurochemistry, 60(2), 559-565.