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Pharmacol Toxicol. 1999 Mar;84(3):135-42.

The modulatory effect of spermine on the glutamate-NMDA receptor is regionally variable in normal human adult cerebral cortex.

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Department of Biochemistry, University of Queensland, Brisbane, Australia.


The MK-801, glutamate and polyamine binding sites on the N-methyl-D-aspartate class of glutamate receptors labelled with [3H]MK-801 were characterized in four cortical areas (sensorimotor, superior temporal, mid-frontal and occipital) from seven human adult control cases. Age, post-mortem delay, tissue storage time and sex had no significant effects on any of the parameters measured. Dissociation constants (K(D) values) for MK-801 showed similar mean values in the four cortical areas, whereas receptor densities (B(max) values) showed significant differences between sensorimotor or occipital and superior temporal or mid-frontal cortex. There were marked regional differences in the profiles of the spermine- and glutamate-incremented enhancement of specific [3H]MK-801 binding. The EC(50) for the glutamate enhancement was significantly higher in the occipital than in the mid-frontal and sensorimotor cortex, whereas maximal glutamate-enhanced binding values did not differ. The maximal enhancement of [3H]MK-801 binding by spermine and glutamate varied between the cases, ranging from zero to 40.4+/-9.3 fmol x mg protein(-1) for spermine, and from 85+/-5 to 111+/-10 fmol x mg protein(-1) for glutamate. Maximal spermine enhancement of [3H]MK-801 binding was significantly more variable in superior temporal or mid-frontal than in sensorimotor or occipital cortex. The results suggest that N-methyl-D-aspartate receptor sites, especially the polyamine site, are heterogeneous in human cerebral cortex, and show a high degree of regional and individual variability.

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