Modulation of Cholecystokinin Concentrations in the Rat Hippocampus by Chelation of Heavy Metals

Previously, we have reported that enkephalins, cholecystokinin, and heavy metals show roughly parallel distributional patterns in the hippocampus. A substantial body of evidence indicates that cholecystokinin-octapeptide (CCK-8) and enkephalins act as neurotransmitters. A CCK-8 degrading enzyme was...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1984-09, Vol.81 (18), p.5876-5880
Main Authors: Stengaard-Pedersen, K., L.-I. Larsson, Fredens, K., Rehfeld, J. F.
Format: Article
Language:English
Subjects:
Animals
Chelation
Cholecystokinin - metabolism
Ditiocarb - pharmacology
Enzymes
Heavy metals
Hippocampus
Hippocampus - drug effects
Hippocampus - metabolism
Histocytochemistry
Male
Neuropil
Pyramidal cells
Rats
Rats, Inbred Strains
Silver
Sincalide - metabolism
Staining and Labeling
Sulfides
Thiocarbamates - pharmacology
Zinc
Zinc - metabolism
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Summary:Previously, we have reported that enkephalins, cholecystokinin, and heavy metals show roughly parallel distributional patterns in the hippocampus. A substantial body of evidence indicates that cholecystokinin-octapeptide (CCK-8) and enkephalins act as neurotransmitters. A CCK-8 degrading enzyme was recently detected in brain synaptosomes. Its activity depended on free thiol groups and the presence of a heavy metal. Since the heavy metal-containing neuropil is closely related to CCK-immunoreactive nerve terminals, we have investigated the effect of metal chelation on CCK components in the rat hippocampus. In vivo treatment of rats with a single dose of the chelating agent diethyldithiocarbamate caused a reversible chelation of heavy metals in the hippocampus. This effect was paralleled by a 3-fold increase in hippocampal content of CCK-8 and a smaller increase in the intermediate forms of CCK (CCK-58, CCK-39, CCK-33). Diethyldithiocarbamate also decreased the spontaneous motility and aggressiveness of the rats. These data show reversible changes of neuronal CCK processing by a drug, and hence they provide additional evidence that CCK is involved in the regulation of neuronal activities.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.81.18.5876