Comparison of L-[3H]glutamate, D-[3H]aspartate, DL-[3H]AP5 and [3H]NMDA as ligands for NMDA receptors in crude postsynaptic densities from rat brain |
| |
| Authors: | A C Foster G E Fagg |
| |
| Affiliation: | 1. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA;2. Clinical Memory Research Unit, Lund University, VO Minnessjukdomar, Simrisbanv 14/4, 212 24 Malmö, Sweden;3. Memory Clinic, Skåne University Hospital, Inga Marie Nilssons gata 47, 214 21 Malmö, Sweden;4. Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany;5. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC 3052, Australia;6. The Commonwealth Scientific and Industrial Research Organisation/Australian E-Health Research Centre, Butterfield St & Bowen Bridge Rd, Herston, QLD 4029, Australia;7. Roche Diagnostics GmbH, Sandhofer Str. 116, 68305 Mannheim, Germany;8. Roche Diagnostics GmbH, Inselkammerstraße 8, 82008 Unterhaching, Munich, Germany;9. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Göteborgsvägen 31, 431 80 Mölndal, Sweden;10. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Wallinsgatan 6, 431 41 Mölndal, Sweden |
| |
| Abstract: | L-[3H]Glutamate, D-[3H]aspartate, DL-[3H]2-amino-5-phosphonovalerate (AP5) and [3H]N-methyl-D-aspartate (NMDA) were evaluated as radioligands using postsynaptic density (PSD) preparations from rat brain. L[3H]Glutamate had the highest affinity and greatest percentage specific binding, followed by D-[3H]aspartate greater than DL-[3H]AP5 greater than [3H]NMDA. The pharmacological specificity of the binding of each radioligand indicated an interaction with NMDA-preferring receptors, the order of potency of displacing compounds tested being L-glutamate greater than D-aspartate greater than D-AP5 greater than DL-AP5 greater than ibotenate greater than NMDLA greater than quisqualate. For L-[3H]glutamate, the data revealed an interaction with two sites, the major one having NMDA receptor characteristics and the minor one resembling the quisqualate-preferring receptor. Against L-[3H]glutamate binding, quisqualate showed a two-component inhibition profile with an affinity of 25 microM at the NMDA site and 0.19 microM at the quisqualate site. Thus, by using several radioligands possessing activity at NMDA receptors, we confirm that an NMDA receptor binding site is present in crude PSDs. Although it is less selective than D-[3H]aspartate, DL-[3H]AP5 and [3H]NMDA, L-[3H]glutamate remains, by virtue of its high affinity, the ligand of choice for the study of NMDA receptors in preparations where such sites predominate. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
