title: Modulation of cholecystokinin concentrations in the rat hippocampus by chelation of heavy metals.
abstract: 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.
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D004050:Ditiocarb / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006651:Histocytochemistry; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000378:metabolism; D013194:Staining and Labeling; D013859:Thiocarbamates / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism*
chemical_list: D013859:Thiocarbamates; D002766:Cholecystokinin; D004050:Ditiocarb; D015032:Zinc; D012844:Sincalide