Compensatory alterations in receptor-stimulated phosphoinositide hydrolysis in the hippocampus vary as a function of dose of colchicine.
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.
Bonner
M J
MJ
Curriculum in Toxicology, University of North Carolina, Chapel Hill.
Tilson
H A
HA
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003078:Colchicine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006868:Hydrolysis; D007051:Ibotenic Acid / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values
D010716:Phosphatidylinositols; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D007294:Inositol; D016202:N-Methylaspartate; D002217:Carbachol; D003078:Colchicine; D009638:Norepinephrine