Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. I. Saturable sequestration

Journal Article · Wed May 01 00:00:00 EDT 1991 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:5760557

Zaczek, R; Culp, S; Goldberg, H; Mccann, D J; De Souza, E B ^[1]

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1. Addiction Research Center, Baltimore, MD (USA)

Previous studies have identified a saturable site of d-({sup 3}H)amphetamine sequestration (AMSEQ) in rat brain synaptosomes. The present study characterized AMSEQ with respect to its subcellular, neuronal and regional distributions, ontogenetic development, pharmacological specificity and factors required for its maintenance. Although AMSEQ was reduced when assays were performed in Krebs' buffer incubated at 37{degree}C as compared to assays performed in isotonic Tris-sucrose buffer incubated at room temperature, the pharmacological profiles of AMSEQ were virtually identical under both conditions. AMSEQ was negligible in tissues outside the central nervous system, enriched in synaptosomes and partially reduced by striatal kainic acid lesion, indicating neuronal localization. The distribution of AMSEQ in the central nervous system was heterogenous. Highest levels were present in hypothalamus with progressively lower levels noted in parietal cortex, frontal cortex, striatum, thalamus, hippocampus, midbrain, cerebellum, pons-medulla and spinal cord. With regard to its ontogeny, AMSEQ increased early in neonatal life, reaching adult levels by postnatal day 14. Although the effects of amphetamine to abolish the transynaptosomal pH gradient suggest a possible role for this gradient in the maintenance of AMSEQ, the pharmacological profile of AMSEQ indicates that other factors are involved. An interaction with an intrasynaptosomal acid, such as N-acetylaspartate, may account for AMSEQ maintenance. AMSEQ did not possess a stereospecific preference for either d-(IC50 = 177 microM) or I-amphetamine (IC50 = 173 microM). However, the pharmacological profile of AMSEQ indicated structural specificity with antidepressants being relatively potent inhibitors. (Abstract Truncated)

• OSTI ID: 5760557
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Vol. 257:2; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMPHETAMINES
PHARMACOLOGY
BRAIN
METABOLISM
MOLECULAR STRUCTURE
NERVE CELLS
RATS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANALEPTICS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
DISTRIBUTION
DRUGS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MAMMALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
RODENTS
SOMATIC CELLS
SYMPATHOMIMETICS
VERTEBRATES
550501* - Metabolism- Tracer Techniques