Neurochemical, pharmacological, and developmental studies on cerebellar receptors for dicarboxylic amino acids

Journal Article · Sun Jan 01 00:00:00 EST 1984 · Neurochem. Res.; (United States)

DOI:https://doi.org/10.1007/BF00967661· OSTI ID:6743317

Sharif, N A; Roberts, P J

Specific binding of L-(/sup 3/H)glutamate ((/sup 3/H)Glu) and L(/sup 3/H)Asp) to cerebellar membranes represented a time-, temperature-, pH- and protein-dependent interaction which was both saturable and reversible. Binding sites for both radioligands appeared maximally enriched in synaptosomal fractions isolated by gradient centrifugation. Kinetically derived dissociation constant (K/sub off//K/sub on/ . K/sub d/) for (/sup 3/H)Glu binding to this fraction indicated high-affinity (433 nM). Competition experiments employing analogs of excitatory amino acids, including new antagonists, helped identify binding sites for (/sup 3/H)Glu and (/sup 3/H)Asp as receptors with differential pharmacological specificities. Membrane freezing reduced numbers of both receptor types, but binding activity could be recovered partially by incubation at 37 degrees C. Glu receptors exhibited a pronounced deleterious sensitivity to thiol modifying reagents and L-Glu (50-1000 microM) provided protection against these compounds during co-incubation with cerebellar membranes. It is suggested that cold storage may induce partially reversible receptor inactivation by promoting sulfhydryl group/bond modification. Rat cerebellar glutamatergic function (endogenous Glu content, Glu uptake and receptor sites) exhibited an apparent ontogenetic peak between days 8-12 postpartum with a plateauing profile from day 30 to adulthood. The accelerated development (days 8-12) coincides with the first demonstrable Glu release and kainic acid neurotoxicity, as described previously.

• Research Organization: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore
• OSTI ID: 6743317
• Journal Information: Neurochem. Res.; (United States), Vol. 9:1
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ASPARTIC ACID
BIOCHEMICAL REACTION KINETICS
RECEPTORS
CEREBELLUM
ONTOGENESIS
GLUTAMIC ACID
CELL MEMBRANES
NEUROREGULATORS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINO ACIDS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
BRAIN
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DRUGS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MEMBRANES
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
REACTION KINETICS
550801* - Morphology- Tracer Techniques
550201 - Biochemistry- Tracer Techniques