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|Title:||Crucial role of kainate receptors in mediating striatal kainate injection-induced decrease in acetylcholine M1receptor binding in rat forebrain||Authors:||Jin, S.
|Issue Date:||2000||Citation:||Jin, S., Yang, J., Wong, P.T.H., Lee, W.L. (2000). Crucial role of kainate receptors in mediating striatal kainate injection-induced decrease in acetylcholine M1receptor binding in rat forebrain. Brain Research 882 (1-2) : 128-138. ScholarBank@NUS Repository. https://doi.org/10.1016/S0006-8993(00)02857-2||Abstract:||We investigated the roles of kainate-, α-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA)- and N-methyl-d-aspartate (NMDA)-receptors in mediating striatal kainate injection-induced decrease in the binding of acetylcholine M1 receptors in rat forebrain. After unilateral intrastriatal injection of kainate (4 nmol), the bindings of [3H]kainate (10 nM), [3H]MK-801 (4 nM) and [3H]pirenzepine (4 nM) to the rat ipsilateral forebrain membranes declined, reaching the lowest on day 2 to 4 and recovering on day 8. Saturation binding studies, performed on day 2 post-injection, showed that kainate (1, 2, 4 nmol) dose-dependently decreased B(max) and K(d) of the three ligands. (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a selective NMDA receptor channel blocker, antagonised (from a dose of 4 nmol) kainate-induced decreases in the bindings of [3H]kainate (up to ~20%), [3H]MK-801 (up to ~90%) and [3H]pirenzepine (up to ~70%). In contrast, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-NMDA receptor antagonist, almost completely abolished (from a dose of 12 nmol) kainate-induced decreases in the bindings of all the three ligands (up to ~95-98%). Cyclothiazide, a selective potentiator that enhances AMPA receptor-mediated responses, significantly enhanced (from a dose of 4 nmol) kainate-induced decrease in the binding of [3H]kainate but not that of [3H]pirenzepine or [3H]MK-801. In summary, these results indicate that striatal kainate injection-induced decrease in the binding of acetylcholine M1 receptors in rat forebrain is dependent on activation of kainate receptors and, to a certain extent, a consequent involvement of NMDA receptors. These and previous studies provide some evidence showing that kainate receptors might play a crucial role in regulating excitatory amino acids (EAA)-modulated cholinergic neurotransmission in the central nervous system (CNS). (C) 2000 Elsevier Science B.V.||Source Title:||Brain Research||URI:||http://scholarbank.nus.edu.sg/handle/10635/32130||ISSN:||00068993||DOI:||10.1016/S0006-8993(00)02857-2|
|Appears in Collections:||Staff Publications|
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