Pharmacological characterization of [3H]MK-801 binding in the rat spinal cord.
Using a receptor binding assay for [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-10-imi ne (MK-801) the pharmacology of spinal cord NMDA receptors was compared to that of NMDA receptors in the cerebral cortex. The affinities of glutamate site agonists L-glutamate, L-aspartate, ibotenic acid, NMDA and quinolinic acid for stimulation of [3H]MK-801 binding were 6-10 times lower in the spinal cord and the efficacy of quinolinic acid was 50% of that of the other agonists in this region. Also the affinities of glycine site agonists glycine, D-serine, D-alanine and L-serine were lower in the spinal cord as were the affinities of the non-competitive antagonists phencyclidine, (+/-)-cyclazocine and dextromethorphan. The divalent cations Zn2+, Mg2+ and Ca2+ had 4-8 times lower affinity for spinal NMDA receptors while the affinity of Co2+ was 50 times lower. The affinity of [3H]MK-801 was 2.5-fold lower in the spinal cord. These data show that spinal cord NMDA receptors show qualitative and quantitative differences compared to those in the cerebral cortex.
Souverbie
F
F
Division of Geriatric Medicine, Karolinska Institutet, Huddinge University Hospital, Sweden.
Mo
L L
LL
Liu
Y
Y
von Euler
G
G
Sundstr-om
E
E
D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002413:Cations, Divalent; D002540:Cerebral Cortex / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
D000600:Amino Acids, Dicarboxylic; D002413:Cations, Divalent; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C035261:(alpha-carboxycyclopropyl)glycine; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D005998:Glycine