Abstract：
:The GABA type A receptor (GABA(A)R) is the major inhibitory receptor in the mammalian central nervous system and the target of numerous pharmaceuticals. The alpha-subunit of these pentameric Cys-loop neurotransmitter-gated ion channels contributes to the binding of both GABA and allosteric modulators such as the benzodiazepines, suggesting a role for this subunit in the conformational changes associated with activation of the receptor. Herein we use the nonsense suppression methodology to incorporate a photoactivatable unnatural amino acid and photochemically cleave the backbone of the alpha subunit of the alpha(1)beta(2) GABA(A)R in a linker region that is believed to span the subunit. Proteolytic cleavage impairs GABA but not pentobarbital activation, strongly suggesting that conformational changes involving this linker region are critical to the GABA activation pathway.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Hanek AP,Lester HA,Dougherty DAdoi
10.1124/mol.109.059832subject
Has Abstractpub_date
2010-07-01 00:00:00pages
29-35issue
1eissn
0026-895Xissn
1521-0111pii
mol.109.059832journal_volume
78pub_type
杂志文章abstract：:Large conductance, Ca(2+)-activated K+ channels are believed to underlie interburst intervals and, thus, contribute to the control of hormone release from neurohypophysial terminals. Because ethanol inhibits the release of vasopressin and oxytocin, we studied its effects on large conductance, Ca(2+)-activated K+ chann...
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doi：
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-10-01 00:00:00
abstract：:Prenatal exposure to diethylstilbestrol (DES) is known to cause an increased susceptibility to a wide array of clinical disorders in humans. Previous studies from our laboratory demonstrated that prenatal exposure to DES induces thymic atrophy and apoptosis in the thymus. In the current study, we investigated if such ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.096743
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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更新日期：2001-05-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
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pub_type： 杂志文章
doi：10.1124/mol.64.6.1494
更新日期：2003-12-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.096446
更新日期：2015-07-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-04-01 00:00:00
abstract：:Specific toxic and biochemical responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human thymic epithelial (TE) cells in culture are mediated by the TCDD receptor protein. Characterization of the physicochemical properties of the TCDD receptor in cytosol fractions from cultured human TE cells indicates...
journal_title：Molecular pharmacology
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doi：
更新日期：1989-05-01 00:00:00
abstract：:Very few antagonists have been identified for the human pregnane X receptor (PXR). These molecules may be of use for modulating the effects of therapeutic drugs, which are potent agonists for this receptor (e.g., some anticancer compounds and macrolide antibiotics), with subsequent effects on transcriptional regulatio...
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journal_title：Molecular pharmacology
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doi：10.1124/mol.108.054312
更新日期：2009-06-01 00:00:00
abstract：:Structural changes in the macromolecular targets of pharmacological agents can result in alterations in the efficacy of these agents. In previous studies, we identified a variant structural form of thymidylate synthase (TS) that is associated with relative resistance to 5-fluoro-2'-deoxyuridine, in a human colonic tum...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-08-01 00:00:00
abstract：:G protein activation by different mu-selective opioid agonists was examined in rat thalamus, SK-N-SH cells, and mu-opioid receptor-transfected mMOR-CHO cells using agonist-stimulated guanosine-5'-O-(gamma-thio)-triphosphate ([35S]GTP gamma S) binding to membranes in the presence of excess GDP. [D-Ala2, N-MePhe4, Gly5-...
journal_title：Molecular pharmacology
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doi：10.1124/mol.51.1.87
更新日期：1997-01-01 00:00:00
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更新日期：2021-01-12 00:00:00
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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doi：
更新日期：1985-07-01 00:00:00
abstract：:Obesity is now recognized as a rapidly increasing worldwide threat to health, largely as a result of causing diabetes. Thus, considerable efforts are underway in the pharmaceutical industry to find drugs to treat this condition. Target validation in various academic and industrial laboratories has revealed a number of...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
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更新日期：2006-09-01 00:00:00
abstract：:The human mu-opioid receptor (HmuOR) is a G-protein coupled receptor that mediates analgesia, euphoria and other important central and peripheral neurological functions. In this study, we found in a yeast two-hybrid screen that a protein kinase C-interacting protein (PKCI) specifically interacts with the C terminus of...
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更新日期：2004-11-01 00:00:00
abstract：:Nuclear receptors play important roles in the maintenance of the endocrine system, regulation of organ differentiation, and fetal development. Endocrine disruptors exert their adverse effects by disrupting the endocrine system via various mechanisms. To assess the effects of endocrine disruptors on nuclear receptors, ...
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更新日期：2005-03-01 00:00:00
abstract：:The liver is the only solid organ that can respond to major tissue loss or damage by regeneration to restore liver biomass. The aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can disrupt the regenerative process, as evidenced by suppression of DNA synthesis in rat primary hepatocyte...
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更新日期：2003-02-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
更新日期：1991-12-01 00:00:00
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doi：
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abstract：:The aim of the current study is to determine whether butein (3,4,2',4'-tetrahydroxychalcone) exhibits antiproliferative effects against tumor cells through suppression of the signal transducer and activator of transcription 3 (STAT3) activation pathway. We investigated the effects of butein on constitutive and inducib...
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