Developmental changes in the sensitivity of the N-methyl-D-aspartate receptor to polyamines.
The binding of [125I]I-MK-801 to N-methyl-D-aspartate (NMDA) receptors on membranes prepared from cultured cerebral cortical neurons and from forebrain of rats of different ages was investigated. Specific binding of [125I]I-MK-801 was enhanced by glutamate, glycine, and polyamines and was inhibited by divalent cations and open-channel blockers of the NMDA receptor, indicating that [125I]I-MK-801 selectively labels a component of the NMDA receptor/ion channel complex. The ability of spermine to enhance the binding of [125I]I-MK-801 was lower in membranes prepared from cultured cerebral cortical neurons or from neonatal rat brain than in membranes prepared from adult rat brain. There was a progressive increase in the potency of spermine and in the magnitude of the stimulatory effect of spermine in rat forebrain between days 3 and 10 of postnatal life. In contrast, the apparent affinity of the NMDA receptor for spermine remained unchanged in cerebral cortical neurons maintained in culture for up to 5 weeks. Mg2+ also enhanced the binding of [125I]I-MK-801 and was more potent in membranes prepared from adult than from 3-day-old rat forebrain. The potency of glutamate for enhancing the binding of [125I]I-MK-801 was not altered in 3-day-old, compared with adult, brain tissue. The increase in the affinity of the polyamine recognition site on the NMDA receptor complex in rat forebrain during the first 2 weeks of postnatal life suggests that the macromolecular properties of the NMDA receptor are altered during development. This may suggest that the subunit composition of the NMDA receptor is under developmental control. Cultured cortical neurons may represent a useful system for investigating factors that regulate developmental changes in the properties of the NMDA receptor.
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.
K
K
Williams
J L
JL
Hanna
P B
PB
Molinoff
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology
D005971:Glutamates; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D008274:Magnesium; D005998:Glycine