Washable endogenous substances and regional heterogeneity in agonist enhanced [3H]MK-801 binding in rat brain. 1996

L McCoy, and E K Richfield
Department of Psychiatry, University of Rochester, School of Medicine and Dentistry, NY 14642, USA.

NMDA receptor/ion channel function is modulated through a number of distinct sites that regulate channel opening. Published studies report widely varying results in modulatory site agonist effects due to assay conditions and technique. Also, NMDA receptor regulation at these sites by endogenous substances remains poorly characterized. The objectives of the present study in Sprague-Dawley rat forebrain sections were: (i) determine the contribution of various prewash variables on agonist stimulation of the NMDA receptor, (ii) compare regional differences in functional glycine, spermidine and NMDA binding sites under optimized prewash conditions, and (iii) define the influence of endogenous substances at each modulatory site by analyzing changes in binding at different prewash durations. We demonstrate that prewash conditions have a critical influence on [3H]MK-801 binding in rat tissue sections and that this effect was differentially expressed across brain regions. An extended prewash duration caused a regionally specific decrease in unenhanced [3H]MK-801 binding, while a short prewash caused a regionally specific biphasic effect on enhanced [3H]MK-801 binding. After prolonged prewash, binding was restored to previous (unwashed) binding levels with exogenously added glycine, NMDA, or spermidine alone or combinations of agonists. These data suggest that washable endogenous substances contribute to the full functionality of the NMDA receptor and the regional heterogeneity in [3H]MK-801 binding is dependent on the interaction of receptor protein subtypes and the presence of one or more endogenous substances.

UI MeSH Term Description Entries
D007507 Therapeutic Irrigation The washing of a body cavity or surface by flowing water or solution for therapy or diagnosis. Douching,Lavage,Douchings,Irrigation, Therapeutic,Irrigations, Therapeutic,Lavages,Therapeutic Irrigations
D008297 Male Males
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005998 Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Aminoacetic Acid,Glycine, Monopotassium Salt,Glycine Carbonate (1:1), Monosodium Salt,Glycine Carbonate (2:1), Monolithium Salt,Glycine Carbonate (2:1), Monopotassium Salt,Glycine Carbonate (2:1), Monosodium Salt,Glycine Hydrochloride,Glycine Hydrochloride (2:1),Glycine Phosphate,Glycine Phosphate (1:1),Glycine Sulfate (3:1),Glycine, Calcium Salt,Glycine, Calcium Salt (2:1),Glycine, Cobalt Salt,Glycine, Copper Salt,Glycine, Monoammonium Salt,Glycine, Monosodium Salt,Glycine, Sodium Hydrogen Carbonate,Acid, Aminoacetic,Calcium Salt Glycine,Cobalt Salt Glycine,Copper Salt Glycine,Hydrochloride, Glycine,Monoammonium Salt Glycine,Monopotassium Salt Glycine,Monosodium Salt Glycine,Phosphate, Glycine,Salt Glycine, Monoammonium,Salt Glycine, Monopotassium,Salt Glycine, Monosodium
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
D001345 Autoradiography The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed) Radioautography
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013095 Spermidine A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine.
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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