Regulation of gamma-aminobutyric acidA receptor subunit expression by activation of N-methyl-D-aspartate-selective glutamate receptors.

Article date: 1991/5/1

PubMed ID: 1674584

Journal name: Molecular pharmacology (ISSN: 0026-895X)


Exposure of primary cultures of rat cerebellar granule cells to specific antagonists of the N-methyl-D-aspartate (NMDA)-selective glutamate receptor reduces the steady state levels of mRNAs encoding various gamma-aminobutyric acidA (GABAA) receptor subunits. These neurons are glutamatergic and require a depolarizing concentration of K+ (25 mM) for optimal development and survival. When the neuronal differentiation rate is retarded by lowering of the extracellular [K+] (to 12.5 mM), a persistent stimulation of the same glutamate receptors with nonneurotoxic doses of NMDA increases the expression of these GABAA receptor subunits. This suggests that the lowered K+ concentration reduces neuronal depolarization and the consequent release of glutamate from the cells. These results show that the neuronal content of selected GABAA receptor subunit mRNAs is optimized by certain levels of glutamate in the culture medium, suggesting a neurotrophic action of this neurotransmitter at certain developmental stages of granule cells in culture.

Author List: Memo M, Bovolin P, Costa E, Grayson D R

Publication Types: Journal Article

Substances mentioned in the article: Glutamates; Quinoxalines; RNA, Messenger; Receptors, GABA-A; Receptors, Glutamate; Receptors, Neurotransmitter; Muscimol; Glutamic Acid; gamma-Aminobutyric Acid; N-Methylaspartate; Dizocilpine Maleate; 6-Cyano-7-nitroquinoxaline-2,3-dione;

Mesh terms: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Base Sequence; Dizocilpine Maleate/pharmacology; Dose-Response Relationship, Drug; Down-Regulation/physiology; Gene Expression Regulation/drug effects; Glutamates/pharmacology; Glutamic Acid; Molecular Sequence Data; Muscimol/pharmacology; N-Methylaspartate/pharmacology; Polymerase Chain Reaction; Quinoxalines/pharmacology; RNA, Messenger/genetics; Rats; Rats, Inbred Strains; Receptors, GABA-A/genetics; Receptors, Glutamate; Receptors, Neurotransmitter/antagonists & inhibitors; gamma-Aminobutyric Acid/pharmacology;

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