Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro.
The properties of many ligand-gated ion channels are altered during development. We have characterized a developmental switch in the sensitivity of NMDA receptors to the novel antagonist ifenprodil using ligand binding assays with rat brain membranes and voltage-clamp recording of Xenopus oocytes expressing NMDA receptors after injection of RNA from rat brain and from cloned subunits of the receptor. In neonatal rat brain, NMDA receptors have a uniformly high affinity for ifenprodil. During postnatal development, a second population of receptors having a 100-fold lower affinity for ifenprodil is expressed and represents 50% of NMDA receptors in adult rat brain. This developmental change also occurred in cortical neurons maintained in primary culture. Ifenprodil potently inhibited responses of homomeric NR1 and heteromeric NR1/NR2B receptors but not NR1/NR2A receptors expressed in oocytes, suggesting that inclusion of different NR2 subunits in native NMDA receptors can control the sensitivity to ifenprodil.
Williams
K
K
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.
Russell
S L
SL
Shen
Y M
YM
Molinoff
P B
PB
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism; D003001:Cloning, Molecular; D016291:Dizocilpine Maleate / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014982:Xenopus laevis
D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; C010739:ifenprodil