Ethanol-mediated inhibition of mitogen-activated protein kinase phosphorylation in mouse brain.
Ethanol (1.5-3.5 g/kg body weight) was administered intraperitoneally to mice and the phosphorylation of MAP (mitogen-activated protein) kinase in the cerebral cortex was determined using phospho-specific MAP kinase antibodies. Ethanol inhibited the phosphorylation of MAP kinase in a dose- and time-dependent manner. Developmental studies demonstrated that the levels of phospho-MAP kinase increased from fetal cortex (prenatal) to 16-day-old mice (postnatal) and remained constant up to 4 months of age. However, ethanol (3.5 g/kg) decreased the phospho-MAP kinase staining in all of the age groups studied. Subcellular fractionation studies demonstrated that ethanol inhibited the phosphorylation of MAP kinase in both the cytosol as well as nucleus, but did not alter the levels of MAP kinase. Likewise, MK-801 (0.4 mg/kg) or flurazepam (75 mg/kg) also decreased the phospho-MAP kinase content. These data indicate that ethanol may inhibit the phosphorylation of MAP kinase in vivo by either inhibiting NMDA receptors or activating GABA receptors.
Kalluri
Haviryaji S G
HS
Department of Pharmacology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX 78229-3900, USA.
Ticku
Maharaj K
MK
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005479:Flurazepam / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors
D018757:GABA Modulators; D018696:Neuroprotective Agents; D000431:Ethanol; D016291:Dizocilpine Maleate; D020928:Mitogen-Activated Protein Kinases; D005479:Flurazepam