Molecular cloning, functional expression, and pharmacological characterization of an N-methyl-D-aspartate receptor subunit from human brain.
A cDNA encoding a full-length N-methyl-D-aspartate (NMDA) receptor subunit 1, hNR1, was isolated from a human brain cDNA library. The hNR1 cDNA encodes an open reading frame of approximately 2.7 kb that shares high homology with the rat brain NMDA receptor subunit 1 and the mouse zeta 1 subunit. The hNR1 sequence, however, diverges from the rodent and murine homologs near the C terminus, suggesting that they represent alternatively spliced messages of the same gene. Oocytes injected with cRNA synthesized from the hNR1 cDNA express glutamate and NMDA-activated currents in the presence of glycine. Currents are blocked by the NMDA-receptor-specific antagonists 2-amino-5-phosphovaleric acid and 7-chlorokynurenate, and the open channel blockers MK-801 and phencyclidine, by Mg2+ ions in a voltage-dependent manner, and by Zn2+. Expressed hNR1 homomeric receptor channels exhibit the high Ca2+ permeability characteristic of neuronal NMDA receptors. Therefore, the cDNA clone hNR1 codes for a human brain NMDA receptor subunit cognate to the rodent and murine brain NR1 subunits.
Planells-Cases
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Department of Biology, University of California, San Diego, La Jolla 92093-0319.
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Ferrer-Montiel
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Montal
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D015723:Gene Library; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D016318:Quisqualic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D046911:Macromolecular Substances; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D004247:DNA; D007608:Kainic Acid; D005998:Glycine