METABOTROPIC GLUTAMATE RECEPTORS IN CULTURED CEREBELLAR GRANULE CELLS - DEVELOPMENTAL PROFILE

被引:56
作者
ARONICA, E
CONDORELLI, DF
NICOLETTI, F
DELLALBANI, P
AMICO, C
BALAZS, R
机构
[1] NETHERLANDS INST BRAIN RES,MEIBERGDREEF 33,1105 AZ AMSTERDAM,NETHERLANDS
[2] UNIV CATANIA,SCH MED,INST PHARMACOL,I-95124 CATANIA,ITALY
[3] UNIV CATANIA,SCH MED,INST BIOCHEM,I-95124 CATANIA,ITALY
关键词
METABOTROPIC GLUTAMATE RECEPTORS; PHOSPHOINOSITIDE HYDROLYSIS; CEREBELLAR GRANULE CELLS; DEVELOPMENT; MESSENGER RNA;
D O I
10.1111/j.1471-4159.1993.tb03185.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 [H-3]inositol monophosphate ([H-3]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 [H-3]InsP formation and that this component of the response develops relatively late. Accordingly, NMDA-induced [H-3]InsP formation, estimated under Mg2+-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 approximately 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.
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收藏
页码:559 / 565
页数:7
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