ISSN:
1573-6903
Keywords:
NMDA
;
[3H]MK-801
;
dog brain
;
spinal cord
;
rodent brain
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The biochemical and pharmacological properties of [3H]MK-801 binding to the N-methyl-d-aspartate (NMDA) receptor-channel in homogenates of mouse, guinea pig and dog brain, dog cerebral cortex and rat spinal cord were determined using radioligand binding techniques. Specific [3H]MK-801 binding increased linearily with increasing tissue concentration and in general represented 80–93% of the total binding at 6–8 nM radioligand concentration. [3H]MK-801 interacted with brain and spinal homogenates with high affinity. The dissociation constants (K d ) for all tissues studied were similar ranging between 7.9 and 11.9 nM, whereas the maximum number of binding sites (Bmax) showed a wide, tissue-dependent range (0.1–6.75 pmol/mg protein). The rank order of tissue enrichment was found to be as follows: mouse brain〉〉dog cerebral cortex〉〉dog brain〉〉 guinea pig brain〉〉rat spinal cord. Specific [3H]MK-801 binding in rodent and dog brain, dog cerebral cortex and rat spinal cord exhibited a similar pharmacological profile 9correlation coefficients=0.93–0.99). The rank order of potency of unlabelled compounds competing for [3H]MK-801 binding was: (+)MK-801〉(−)MK-801〉phencyclidine〉(−)cyclazocine〉〉(+)cyclazocine ≥ ketamine〉(+)N-allyl-N-normetazocine〉(−)N-allyl-N-normetazocine〉(−)pentazocine〉(+)pentazocine. NMDA, Kainate, quisqualate and several other compounds failed to inhibit [3H]MK-801 binding at 100 μM. In modulation studies conducted on extensively washed dog cortex membranes, Mg2+ ions stimulated [3H]MK-801 binding at 10 μM-1 mM (EC50=91.5 μM) and then inhibited the binding from 1 mM to 10 mM (IC50=3.1 mM). Glycine stimulated [3H]MK-801 binding at 30 nM-1 mM (EC50=256 nM). In contrast, Zn2+ ions inhibited the binding of [3H]MK-801 binding site exhibited similar pharmacological and biochemical properties. These data appear to suggest that the pharmacological profile of the NMDA-receptor-channel is species and tissue independent.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00974875
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