Dissociation between changes in glutamate receptor binding sites and their coupling to phosphatidylinositol metabolism following intrahippocampal colchicine injection.
Intrahippocampal colchicine injection produces a rapid death of granule cells and pyramidal neurons in the hippocampus in the rat. Under the appropriate assay conditions, [3H]glutamate labels the N-methyl-D-aspartate type of glutamate receptors while [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate labels the quisqualate type. Unilateral injection of colchicine (15 micrograms) in the dorsal hippocampus did not produce any change in [3H]glutamate and [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate binding in membrane fractions from the dentate gyrus or CA1 field contralateral to the injection side, at least up to 12 days after the injection. However, it produced a progressive decrease in the binding of both ligands in dentate gyrus and CA1 of the injected hippocampus. In the dentate gyrus the changes in binding as a function of time after the injection were biphasic with a rapid exponential decrease (t1/2 about 8 days for both [3H]glutamate and [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) until 12 days after the injection followed by a much slower decrease afterwards. A similar pattern was observed in CA1 although the changes in binding were smaller and delayed by about three days as compared to the dentate gyrus. Kinetic analyses of the binding at equilibrium were performed seven days after the injection and indicated that the changes in [3H]glutamate binding were due to a change in the maximum number of sites but not in affinity for the ligand.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakagawa
Y
Y
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Baudry
M
M
D000818:Animals; D003078:Colchicine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D010069:Oxadiazoles; D010716:Phosphatidylinositols; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D003078:Colchicine