High- and low-affinity NMDA receptor-binding sites in rat spinal cord: effects of traumatic injury.
N-methyl-D-aspartate (NMDA) receptor-mediated events have been implicated in the pathophysiology of posttraumatic spinal cord injury. In the present study, [3H]MK801 was used to analyse the changes in NMDA receptor-binding sites in rat spinal cord after impact trauma at T9. In contrast to brain, which showed only a single binding site, spinal cord showed both high-affinity (Kd1 = 0.47 +/- 0.24 nM) and low-affinity (Kd2 = 7.75 +/- 1.82 nM) binding sites with relatively low binding density (Bmax1 = 0.11 +/- 0.04 pmol/mg protein and Bmax2 = 0.84 +/- 0.11 pmol/mg protein). Time-course studies demonstrated significant decreases in the binding of [3H]MK801 at the thoracic and lumbar segments at 4 h after spinal cord injury with recovery by 24 h. Scatchard analyses indicate that these changes likely involve both high- and low-affinity binding sites. The transitory reduction in [3H]MK801-binding after trauma may reflect downregulation of NMDA receptors as a consequence of posttraumatic glutamate release and may serve to limit excitotoxin-induced injury.
Sun
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Department of Neurology, School of Medicine, Georgetown University, Washington, DC 20007.
Faden
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D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate