Abstract：
:The N-methyl-d-aspartate (NMDA) receptor is a key target of ethanol action in the central nervous system. Alcohol inhibition of NMDA receptor function involves small clusters of residues in the third and fourth membrane-associated (M) domains. Previous results from this laboratory have shown that two adjacent positions in the M3 domain, F636 and F637, can powerfully regulate alcohol sensitivity and ion channel gating. In this study, we report that these positions interact with one another in the regulation of both NMDA receptor gating and alcohol action. Using dual mutant cycle analysis, we detected interactions among various substitution mutants at these positions with respect to regulation of glutamate EC50, steady-state to peak current ratios (Iss:Ip), mean open time, and ethanol IC50. This interaction apparently involves a balancing of forces on the M3 helix, such that the disruption of function due to a substitution at one position can be reversed by a similar substitution at the other position. For example, tryptophan substitution at F636 or F637 increased or decreased channel mean open time, respectively, but tryptophan substitution at both positions did not alter open time. Interestingly, the effects of a number of mutations on receptor kinetics and ethanol sensitivity appeared to depend upon subtle structural differences, such as those between the isomeric amino acids leucine and isoleucine, as they could not be explained on the basis of sidechain molecular volume or hydrophilicity.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Ren H,Zhao Y,Wu M,Dwyer DS,Peoples RWdoi
10.1016/j.neuropharm.2016.11.013subject
Has Abstractpub_date
2017-03-01 00:00:00pages
20-33eissn
0028-3908issn
1873-7064pii
S0028-3908(16)30509-3journal_volume
114pub_type
杂志文章abstract：:Mechanisms underlying stress-induced depression and antidepressant drug action were shown to involve alterations in serotonergic (5-HT) neurotransmission and expression of genes coding for proteins associated with neurotrophic signaling pathways and cell-survival in the hippocampus and cortex. Expression of these gene...
journal_title：Neuropharmacology
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.11.013
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：2018-06-01 00:00:00
abstract：:The effects of phospholipase A2, cyclooxygenase-1, cyclooxygenase-2, and 5-lipoxygenase inhibitors on acute opiate withdrawal induced by selective mu, kappa and delta receptor agonists was investigated in vitro. After a 4 min in vitro exposure to D-Ala2-N-methyl-Phe-Gly5-ol)enkephalin (DAMGO; a highly selective mu ago...
journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
pub_type： 杂志文章
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abstract：:Zatosetron (13 mg or 0.19 mg/kg), a potent and selective 5-HT3 receptor antagonist was studied with a 30 min infusion in a crossover double-blind placebo-controlled trial for acute migraine therapy. Groups receiving zatosetron and placebo were demographically similar and zatosetron was well-tolerated in all patients w...
journal_title：Neuropharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期：1994-03-01 00:00:00
abstract：:N-methyl-D-aspartate (NMDA) receptor antagonists have therapeutic potential in numerous CNS disorders ranging from acute neurodegeneration (e.g. stroke and trauma), chronic neurodegeneration (e.g. Parkinson's disease, Alzheimer's disease, Huntington's disease, ALS) to symptomatic treatment (e.g. epilepsy, Parkinson's ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0028-3908(99)00019-2
更新日期：1999-06-01 00:00:00
