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The metabotropic glutamate receptor (MGR): pharmacology and subcellular location.
The metabotropic glutamate receptor (MGR): pharmacology and subcellular location.
- Source :
-
Journal of physiology, Paris [J Physiol Paris] 1992; Vol. 86 (1-3), pp. 47-55. - Publication Year :
- 1992
-
Abstract
- A pharmacological characterization of the metabotropic glutamate receptor (MGR) was performed in striatal neurons. Among the excitatory amino acid receptor antagonists tested, only D, L-2-amino-3-phosphonopropionate (D, L-AP3) inhibited QA-induced inositol phosphate (InsP) formation in a competitive manner (mean pKi = 4.45 +/- 0.43, n = 4). However, this drug was a partial agonist of MGR since it stimulated the inositol-phosphate formation. We found that D, L-AP3 also inhibited NMDA-induced calcium increase, in a competitive manner (mean pIC50 = 4.34 +/- 0.22, n = 8, and mean pKi = 3.7 +/- 0.11 n = 5). 1 mM of the ionotropic agonists alpha-amino-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate (KA) or domoate (DO) (100 microM or higher) induced a significant InsP formation in striatal neurons. The InsP responses induced by all these agonists were totally blocked by the phorbol ester phorbol-12,13-dibutyrate (PdBu), but not by atropine or prazosin. Agonist-induced increases of intracellular calcium concentrations ([Ca2+]i) were insensitive to PdBu, suggesting that all these substances were able to stimulate the MGR in striatal neurons. Trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD) evoked dose-dependent inositol phosphate formations with an EC50 of 29 microM but had no significant effect on NMDA or AMPA receptors, as measured by the patch clamp technique. In the presence of 30 microM of AMPA, trans-ACPD induced a significant release of arachidonic acid (AA) in striatal neurons. No important AA release was observed by any of these agonists alone. 56 mM K+ did not mimic AMPA in this associative ionotropic/metabotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
- Subjects :
- Animals
Calcium metabolism
Corpus Striatum cytology
Intracellular Membranes metabolism
Mice
Neurons ultrastructure
Osmolar Concentration
Receptors, AMPA metabolism
Receptors, Metabotropic Glutamate antagonists & inhibitors
Corpus Striatum metabolism
Neurons metabolism
Receptors, Metabotropic Glutamate chemistry
Receptors, Metabotropic Glutamate metabolism
Subcellular Fractions metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0928-4257
- Volume :
- 86
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- Journal of physiology, Paris
- Publication Type :
- Academic Journal
- Accession number :
- 1343596
- Full Text :
- https://doi.org/10.1016/s0928-4257(05)80007-5