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National Institute of Environmental Health Sciences

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Publication Detail

Title: Compensatory alterations in receptor-stimulated phosphoinositide hydrolysis in the hippocampus vary as a function of dose of colchicine.

Authors: Bonner, M J; Tilson, H A

Published In Toxicol Lett, (1991 Sep)

Abstract: The stimulation of inositol phospholipid (PI) hydrolysis by various receptor agonists was measured in the hippocampus of rats 12 weeks after various concentrations (0.5-2.0 microgram/site) of colchicine were infused into the dentate gyrus. Colchicine produced a dose-related decrease in the average width and length of the granule cell line; the pyramidal cells in CA1 and CA3 regions of the hippocampus were affected only at higher concentrations of colchicine. Compensatory increases in receptor-mediated hydrolysis of phosphoinositides (PI) in hippocampal slices were seen at 100 microns carbachol and ibotenic acid in rats receiving 1.5-3.5 microgram colchicine/site. Compensatory increases in norepinephrine (100 microns) and N-methyl-D-aspartate (100 microns) stimulated PI were seen at 2.5-3.5 and 3.5 micrograms colchicine/site, respectively. Compensatory increases in PI hydrolysis were not seen in slices from animals receiving 0.5 microgram colchicine/site. These data support the hypothesis that the signal transduction system in the hippocampus undergoes a compensatory change following experimentally induced destruction of dentate gyrus granule cells. In addition, these changes occur for more than one neurotransmitter and the alterations vary as a function of the size of the lesion.

PubMed ID: 1654603 Exiting the NIEHS site

MeSH Terms: Animals; Carbachol/pharmacology; Colchicine/toxicity*; Dose-Response Relationship, Drug; Hippocampus/drug effects; Hippocampus/metabolism*; Hippocampus/pathology; Hydrolysis; Ibotenic Acid/pharmacology; Inositol/metabolism; Male; N-Methylaspartate/pharmacology; Norepinephrine/pharmacology; Phosphatidylinositols/metabolism*; Pyramidal Tracts/drug effects; Pyramidal Tracts/metabolism; Pyramidal Tracts/pathology; Rats; Rats, Inbred F344; Receptors, Neurotransmitter/drug effects; Receptors, Neurotransmitter/physiology*; Reference Values

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