Developmental changes in the inhibitory actions of ethanol on glutamate-induced translocation of protein kinase C in cerebellar granule neurons. 1997

M Barrios, and S Liljequist
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.

The effects of increasing concentrations of ethanol (25-200 mM) on the enhancement of [3H]phorbol-12,13-dibutyrate ([3H]PDBu) binding produced by different glutamate receptor agonists, indicative of a translocation of the intracellular enzyme protein kinase C (PKC), were studied in rat cerebellar granule cells at 2, 4, 8, and 12 days in vitro (DIV). Glutamate-produced stimulation of [3H]PDBu binding was inhibited by 50 mM ethanol at 2 DIV, whereas higher ethanol concentrations (> 100 mM) were needed to reduce the increase of [3H]PDBu binding in cells grown for 4, 8, and 12 DIV. Ethanol significantly inhibited NMDA-stimulated [3H]PDBu binding in a concentration-dependent fashion in cells maintained in culture for 4 and 8 days, respectively, with a slightly less pronounced inhibition by ethanol (50 mM) seen in cells kept for 2 and 12 DIV. Application of higher ethanol concentrations (> 100 mM), inhibited the NMDA-induced stimulation in all cell preparations. Following kainic acid-induced enhancement of [3H]PDBu binding, ethanol (100 mM) reduced the binding only in cells maintained for 2 DIV. Even higher ethanol concentrations (200 mM) inhibited the effects of kainic acid only in cells maintained for 2 and 4 DIV, respectively. Our data suggest that various subclasses of glutamate receptors display a developmentally determined differential sensitivity to ethanol at least in cerebellar granule cells in vitro.

UI MeSH Term Description Entries
D007608 Kainic Acid (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. Digenic Acid,Kainate,Acid, Digenic,Acid, Kainic
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D014316 Tritium The radioactive isotope of hydrogen also known as hydrogen-3. It contains two NEUTRONS and one PROTON in its nucleus and decays to produce low energy BETA PARTICLES. Hydrogen-3,Hydrogen 3

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