NMDA receptors in rat cerebellum and forebrain: subtle differences in pharmacology and modulation.
Binding of [3H]glutamate, [3H]glycine, and the glutamate antagonist [3H]CGS-19755 to NMDA-type glutamate receptors was examined in homogenates of rat forebrain and cerebellum. Most glutamate agonists had a higher affinity at the [3H]glutamate binding site of cerebellar NMDA receptors as compared with forebrain, whereas all the glutamate antagonists examined showed the reverse relationship. The [3H]glycine binding site of forebrain and cerebellar NMDA receptors showed a similar pharmacology in both brain regions. In the cerebellum, however, [3H]glycine bound to a second site with a 10-fold lower affinity and with a pharmacology that resembled that of the glycine/strychnine chloride channel. [3H]-Glutamate binding was not affected by glycine agonists or antagonists, nor was [3H]glycine binding affected by glutamate agonists in either forebrain or cerebellum. Both CGS-19755 and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, glutamate antagonists, reduced [3H]-glycine binding in cerebellum, whereas only CGS-19755 was effective in forebrain. Glycine agonists and antagonists modulated [3H]CGS-19755 binding in forebrain and cerebellum to different extents in the two brain regions. From these studies we conclude that the cerebellar NMDA receptor has a different pattern of modulation at glutamate and glycine sites and that glycine may play a more important role in the control of NMDA function in the cerebellum as compared with forebrain.
Widdowson
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PS
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, England, UK.
Trainor
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Lock
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D000818:Animals; D001665:Binding Sites; D002531:Cerebellum / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000378:metabolism; D005998:Glycine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010875:Pipecolic Acids / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; C053672:selfotel; D016202:N-Methylaspartate; D005998:Glycine