Abstract:
:1. Agonists may act at any one of three sites on the N-methyl-D-aspartate (NMDA) receptor-effector complex to promote opening of the associated ion channel. The three sites are activated by i) NMDA, L-glutamate, aspartate, and other dicarboxylic amino acids; ii) glycine, D-serine, D-cycloserine, and others; iii) the polyamines spermine or spermidine, but not cadaverine or putrescine. 2. This opening by exogenous agonists is reflected by an enhanced binding of the phencyclidine-like dissociative anesthetic [3H]MK-801 to rat cortical membranes (well washed to remove endogenous agonists, e.g., L-glutamate, glycine). 3. The effects of adding combinations of agonists yielded stimulation approximately equal to the sum of each agonist's effect, suggesting that in the first approximation the three classes act at independent sites. 4. When the glutamate (E) site was antagonized with D-2-amino-5-phosphonopentanoate (D-AP5), no stimulation in binding could be elicited by agonists at the two other sites. Activation of the E site is therefore necessary but not sufficient for channel opening. 5. When the glycine (G) site was antagonized with 7-chlorokynurenate, no stimulation in binding could be elicited by agonists at the other two sites. Activation of the G site is therefore necessary but not sufficient for channel opening. 6. Of the two putative antagonists for the polyamine (PA) site, ifenprodil fails to completely inhibit the binding of [3H]MK-801, whereas arcaine inhibited [3H]MK-801 binding completely. We present data which question the selectivity of arcaine for the polyamine site, and propose that the polyamine site is merely modulatory, but neither necessary nor sufficient, for channel opening.
journal_name
Prog Neuropsychopharmacol Biol Psychiatryauthors
Lehmann J,Colpaert F,Canton Hdoi
10.1016/0278-5846(91)90079-gsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
183-90issue
2eissn
0278-5846issn
1878-4216journal_volume
15pub_type
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
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pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章,评审
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
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更新日期:2005-06-01 00:00:00