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Title: Guanyl nucleotide interactions with dopaminergic binding sites labeled by (/sup 3/H)spiroperidol in human caudate and putamen: guanyl nucleotides enhance ascorbate-induced lipid peroxidation and cause an apparent loss of high affinity binding sites

The human caudate and putamen contain two high affinity binding sites for (/sup 3/H)spiroperidol. Both of these affinity states exhibit dopaminergic selectivity. Ascorbic acid, at 0.1 mM, induces a slow loss of the low affinity component of (/sup 3/H)spiroperidol binding in these tissues. The addition of guanyl nucleotides to the ascorbate produces a more rapid loss of (/sup 3/H)spiroperidol binding which includes a loss of the highest affinity state for (/sup 3/H)spiroperidol. Ascorbate induces lipid peroxidation in human caudate and putamen, an effect that is further enhanced by guanyl and inosine nucleotides. In the absence of ascorbate, guanyl nucleotides have no effect on (/sup 3/H)spiroperidol binding but do decrease the affinity of dopamine at each affinity state greater than 60-fold. In the absence of ascorbate, guanyl nucleotides apparently decrease agonist affinity at human brain dopamine2-binding sites without causing an interconversion of agonist affinity states.
Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
5304056
Resource Type:
Journal Article
Resource Relation:
Journal Name: Mol. Pharmacol.; (United States); Journal Volume: 33:2
Research Org:
Case Western Reserve Univ. School of Medicine, Cleveland, OH (USA)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; DOPAMINE; RECEPTORS; LIPIDS; METABOLISM; NUCLEOTIDES; BIOCHEMICAL REACTION KINETICS; SPIPERONE; AFFINITY; ASCORBIC ACID; IN VITRO; MAN; TRACER TECHNIQUES; TRITIUM COMPOUNDS; AMINES; ANIMALS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; CARDIOTONICS; CARDIOVASCULAR AGENTS; DRUGS; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; KINETICS; LABELLED COMPOUNDS; MAMMALS; MEMBRANE PROTEINS; NEUROREGULATORS; ORGANIC COMPOUNDS; PHENOLS; POLYPHENOLS; PRIMATES; PROTEINS; REACTION KINETICS; SYMPATHOMIMETICS; VERTEBRATES; VITAMINS 550201* -- Biochemistry-- Tracer Techniques