Abstract:
:Stimulatory effects of spermine at heteromeric N-methyl-D-aspartate (NMDA) receptors expressed from cloned subunits were studied by voltage-clamp recording in Xenopus oocytes. At NR1A/NR2B receptors, in the presence of a saturating concentration of glycine, the magnitude of spermine stimulation was dependent on the concentration of NMDA or glutamate. In oocytes voltage-clamped at -25 mV, spermine markedly enhanced the response to 10 microM NMDA but had little or no effect on the response to 10 microM NMDA. This effect was not related to the size of the macroscopic currents, the quantity or ratio of injected receptor subunit RNAs, or a voltage-dependent block by spermine. Spermine induced a small (1.2-1.5-fold) decrease in the affinity of NR1A/NR2B receptors for NMDA and glutamate. This decrease was sufficient to counteract the stimulatory effect of spermine at low concentrations of NMDA and glutamate, resulting in no net effect of spermine or a decrease in macroscopic currents in the presence of spermine with low concentrations of agonist. Spermine did not alter the affinity of NR1A/NR2A receptors for NMDA. Endogenous polyamines could act as a bidirectional gain control at some native NMDA receptors containing the NR1A and NR2B subunits, by dampening the response to low concentrations of glutamate and enhancing the response to high concentrations of glutamate. Alternatively, polyamines could enhance the decay of NMDA receptor-mediated responses by increasing the rate of dissociation of glutamate from the receptor.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Williams Ksubject
Has Abstractpub_date
1994-07-01 00:00:00pages
161-8issue
1eissn
0026-895Xissn
1521-0111journal_volume
46pub_type
杂志文章abstract::Serotonin [5-hydroxytryptamine (5-HT)] receptors are distinguished pharmacologically by their characteristic affinities for agonists and antagonists. Two serotonin receptors, the 5-HT2 and 5-HT1c, share a number of pharmacologic and structural properties while differing in their affinities for certain agonists and ant...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
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abstract::Identifying novel mechanisms to enhance glucagon-like peptide-1 (GLP-1) receptor signaling may enable nascent medicinal chemistry strategies with the aim of developing new orally available therapeutic agents for the treatment of type 2 diabetes mellitus. Therefore, we tested the hypothesis that selectively modulating ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.080432
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abstract::We investigated the interactions of the anticancer drug vinorelbine with drug efflux transporters and cytochrome P450 3A drug-metabolizing enzymes. Vinorelbine was transported by human multidrug-resistance associated protein (MRP) 2, and Mrp2 knockout mice displayed increased vinorelbine plasma exposure after oral adm...
journal_title:Molecular pharmacology
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abstract::ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modes...
journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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更新日期:2008-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.63.1.2
更新日期:2003-01-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1124/mol.62.5.1160
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.033928
更新日期:2007-06-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.53.4.613
更新日期:1998-04-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.119.116954
更新日期:2019-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.001313
更新日期:2004-09-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.57.4.738
更新日期:2000-04-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.007161
更新日期:2005-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1124/molpharm.120.000079
更新日期:2021-01-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::Lack of high potency agonists has restricted analysis of the G protein-coupled receptor GPR35. Moreover, marked variation in potency and/or affinity of current ligands between human and rodent orthologs of GPR35 has limited their productive use in rodent models of physiology. Based on the reported modest potency of th...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.089482
更新日期:2014-01-01 00:00:00
abstract::2-Methyl-2-nitrosopropane (MNP) has long been known to undergo photochemical and thermal decomposition, generating di-tert-butyl nitroxide, in organic solvent. The present study was undertaken to demonstrate that MNP can be used as a caged-nitric oxide (NO), which can liberate NO upon illumination. Photolysis of MNP l...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::Cytosolic sulfotransferase (SULT)-mediated sulfation plays an essential role in the detoxification of bile acids and is necessary to avoid pathological conditions, such as cholestasis, liver damage, and colon cancer. In this study, using transgenic mice bearing conditional expression of the activated constitutive andr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.2.292
更新日期:2004-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-06-01 00:00:00
abstract::The effect of lysosomotropic agents and secretory inhibitors were compared with verapamil for their effect on the activity of doxorubicin (DOX) in multiple drug-resistant (MDR) P388 leukemia cells (P388R) and in blocking anthracycline efflux from these cells. Agents known to interact with the plasma membrane did not p...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::Four piperazinoquinolone antibacterial drugs (norfloxacin, ciprofloxacin, enoxacin, and pipemidic acid), known to be gamma-aminobutyric acid (GABA) antagonists, fully reversed the inhibitory effect of GABA on [35S]t-butylbicyclophosphorothionate ([35S] TBPS) binding to rat brain membranes in vitro. Twelve indomethacin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::Intermediate-conductance (KCa3.1) and small-conductance (KCa2) calcium-activated K+ channels are gated by calcium binding to calmodulin (CaM) molecules associated with the calmodulin-binding domain (CaM-BD) of these channels. The existing KCa activators, such as naphtho[1,2-d]thiazol-2-ylamine (SKA-31), 6,7-dichloro-1...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.109421
更新日期:2017-10-01 00:00:00
abstract::Expression of the angiotensin II type 1 receptor (AT1-R) mRNA in vascular smooth muscle cells (VSMC) is down-regulated by a variety of agonists, including growth factors, agonists of Galphaq protein-coupled receptors, and activators of adenylyl cyclase. To determine whether cAMP-dependent protein kinases (PKA) partici...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.54.3.514
更新日期:1998-09-01 00:00:00
abstract::A human recombinant L-type Ca2+ channel (alpha1C,77) was coexpressed with the rat angiotensin AT1A receptor in Xenopus laevis oocytes. In oocytes expressing only alpha1C,77 channels, application of human angiotensin II (1-10 microM) did not affect the amplitude or kinetics of Ba2+ currents (IBa). In sharp contrast, in...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.54.6.1106
更新日期:1998-12-01 00:00:00
abstract::Although much has been learned about the mechanisms of ligand selectivity between different opioid receptor subtypes, little is known about the common opioid binding pocket shared by all opioid receptors. The recently discovered orphanin system offers a good opportunity to study the mechanisms involved in the binding ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.53.4.772
更新日期:1998-04-01 00:00:00
abstract::The endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) bind to G protein-coupled central and peripheral cannabinoid receptors CB1 and CB2, respectively. Due to the relatively high expression of the CB2 isotype on peripheral immune cells, it has been hypothesized that this receptor mediates the immunosuppres...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract::We previously reported that angiotensin II (Ang II) increases cGMP content through a new Ang II receptor subtype that is distinct from both the AT1 and AT2 subtypes in differentiated Neuro-2A cells. In this study, the mechanism of the Ang II-stimulated cGMP increase was investigated in comparison with bradykinin- and ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are synthesized in response to diverse stimuli, including cytokines, growth factors, hormones, and oxidative stress. Here we show that the nitric oxide (NO) donor 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NO) and NO from murine macrophages transcriptionally regulate MMP-13 expressi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.62.4.927
更新日期:2002-10-01 00:00:00