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

Article date: 1991/9/1

PubMed ID: 1654603

Journal name: Toxicology letters (ISSN: 0378-4274)


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.

Author List: Bonner M J, Tilson H A

Publication Types: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Phosphatidylinositols; Receptors, Neurotransmitter; Ibotenic Acid; Inositol; N-Methylaspartate; Carbachol; Colchicine; Norepinephrine;

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

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