Regional mirex distribution and its effects on gamma-aminobutyric acid and flunitrazepam binding in mouse brains

Journal Article · Thu Jan 01 04:00:00 EST 1987 · J. Toxicol. Environ. Health; (United States)

DOI:https://doi.org/10.1080/15287398709531032· OSTI ID:6211620

Leach, J F; Charles, A K

Following ip injection of (/sup 14/C)mirex, its regional distribution was studied parallel to its in vitro effects on (/sup 3/H)-gamma-aminobutyric acid (GABA) and (/sup 3/H)flunitrazepam (FNZ) binding to, and (/sup 3/H)GABA release from, synaptosomes of various mouse brain regions, in order to determine the relationship between relative mirex distribution and its neurotoxic effects mediated through the GABA receptor-ionophore complex. The pattern of mirex uptake into cerebral cortex (CC), brainstem (BS), and cerebellum (CB) showed an initial linear dose-dependent uptake, followed by a decline at higher concentration. The Vmax and Km values determined for the linear mirex uptake phase indicated varied affinities by brain regions, CB and BS being more susceptible to mirex uptake than CC. Both synaptosomal GABA binding and FNZ binding were significantly reduced by mirex in the order of BS approximately equal to CB greater than CC for GABA, and BS approximately equal to CC greater than CB for FNZ. However, mirex lacked any significant effect on the Ca/sup 2 +/-dependent, K+-stimulated release of GABA from radio-prelabeled synaptosomes. While the data indicate no significant differences between brain regions in mirex uptake, they suggest that regional specificities do exist with respect to the inhibition caused by mirex on GABA and FNZ binding to synaptosomes. Unlike the major effects of chlordecone (an analog of mirex) on the dopaminergic system, mirex seems to be primarily neurotoxic through its more specific interaction with the GABA and FNZ binding sites.

• Research Organization: Albany Medical College of Union Univ., NY
• OSTI ID: 6211620
• Journal Information: J. Toxicol. Environ. Health; (United States), Journal Name: J. Toxicol. Environ. Health; (United States) Vol. 21:4; ISSN JTEHD
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFFINITY
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DISTRIBUTION
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HYPNOTICS AND SEDATIVES
INHIBITION
INJECTION
INSECTICIDES
INTAKE
INTRAPERITONEAL INJECTION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MICE
NERVE CELLS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PESTICIDES
REACTION KINETICS
RODENTS
SOMATIC CELLS
TISSUE DISTRIBUTION
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES