Abstract：
:The GABAA receptor belongs, along with the nicotinic acetylcholine receptor, the glycine receptor and the 5-HT3 receptor, to a family of homologous transmitter-gated ion channels mediating fast synaptic transmission. Many classes of drug interact with the GABAA receptor, which is the major inhibitory ion channel in the mammalian brain. Among these drugs are the allosteric modulators acting at the benzodiazepine binding site. In this article, Erwin Sigel and Andreas Buhr discuss recent studies that have identified amino acid residues that are thought to form the binding pocket for these compounds. These residues are probably located at subunit interfaces of the protein pentamer and at least some of them are homologous to residues implicated in channel agonist binding. This implies pseudosymmetry of channel agonist and channel modulatory sites, which may be, as recent data indicate, a general principle realized in other pseudosymmetric protein complexes.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Sigel E,Buhr Adoi
10.1016/s0165-6147(97)01118-8subject
Has Abstractpub_date
1997-11-01 00:00:00pages
425-9issue
11eissn
0165-6147issn
1873-3735pii
S0165-6147(97)01118-8journal_volume
18pub_type
杂志文章,评审abstract：:Drug development consumes huge amounts of time and money and the search for novel analgesics, which are urgently required, is particularly difficult, having resulted in many setbacks in the past. Drug repurposing - the identification of new uses for existing drugs - is an alternative approach, which bypasses most of t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2015.11.006
更新日期：2016-03-01 00:00:00
abstract：:Hypercontraction or abnormal contraction of vascular smooth muscle is a major cause of diseases such as hypertension and vasospasm of the coronary and cerebral arteries. A better understanding of the mechanism of regulation of smooth muscle contraction should lead to improved treatments for such diseases. Recent studi...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01596-0
更新日期：2001-01-01 00:00:00
abstract：:The vascular endothelium is a remarkably heterogeneous organ. In addition to well-characterized anatomical diversity in situ, specific differences are increasingly being recognized between surface antigens on endothelial cells from different tissues, including absence of the classic endothelial marker factor VIII-rela...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(91)90637-8
更新日期：1991-12-01 00:00:00
abstract：:For more than 30 years, WNT/β-catenin and planar cell polarity signaling has formed the basis for what we understand to be the primary output of the interaction between WNTs and their cognate receptors known as Frizzleds (FZDs). In the shadow of these pathways, evidence for the involvement of heterotrimeric G proteins...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.07.001
更新日期：2018-09-01 00:00:00
abstract：:The myeloid-derived suppressor cell (MDSC) is the 'queen bee' of the tumor microenvironment. MDSCs protect the cancer from the patient's immune system, make the tumor resistant to immunotherapy, and allow the tumor to thrive while the patient withers away. Eliminating MDSCs should improve response rates to cancer ther...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.10.008
更新日期：2019-01-01 00:00:00
abstract：:The tachykinin family has recently been extended by the discovery of a third tachykinin gene encoding previously unknown mammalian tachykinins (hemokinin 1, endokinin A and endokinin B) that have a widespread peripheral distribution and a tachykinin NK(1) receptor selectivity. This and the identification of other tach...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2003.11.005
更新日期：2004-01-01 00:00:00
abstract：:Five subtypes of muscarinic acetylcholine receptors have been identified in mammalian tissues, but the selectivity of ligands that are active at these receptors is low. It is possible, however, that selective compounds may be developed by targeting their allosteric site(s). Important new insights into the mechanism of...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)89023-9
更新日期：1995-06-01 00:00:00
abstract：:The genotoxicity of the most potent carcinogen in cigarette smoke [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] is dependent on the relationship between its activation by cytochrome P450 enzymes and its detoxification by carbonyl reduction to NNK alcohol (NNAL) followed by glucuronidation. Recently, '11 beta-...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01090-0
更新日期：1997-08-01 00:00:00
abstract：:Influenza A viral infections claim millions of lives worldwide and continue to impose a major burden on healthcare systems. Current pharmacological strategies to control influenza A virus-induced lung disease are problematic owing to antiviral resistance and the requirement for strain-specific vaccination. The product...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2011.09.001
更新日期：2012-01-01 00:00:00
abstract：:Chronic obstructive pulmonary disease (COPD) is a pulmonary inflammatory disease that is caused by cigarette smoke. The main characteristic of COPD is the continued inflammation caused by the sustained influx of macrophages and neutrophils into the lung. Recent studies have shed light on how these cells are attracted ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2006.09.003
更新日期：2006-11-01 00:00:00
abstract：:Changes in the structure and function of the small airways (<2mm diameter) are now recognized to play a major role in airflow limitation in both chronic obstructive pulmonary disease (COPD) and severe asthma. Increased thickness of the small airway wall causes lumenal narrowing, which can be further occluded by mucus ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2008.04.003
更新日期：2008-07-01 00:00:00
abstract：:Epoxyeicosatrienoic acids (EETs), derived from arachidonic acid by cytochrome P450 epoxygenases, are potent vasodilators that function as endothelium-derived hyperpolarizing factors in some vascular beds. EETs are rapidly metabolized by soluble epoxide hydrolase to form dihydroxyeicosatrienoic acids (DHETs). Recent re...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.11.002
更新日期：2007-01-01 00:00:00
abstract：:The histamine H3 receptor was discovered 15 years ago, and many potent and selective H3 receptor agonists and antagonists have since been developed. Currently, much attention is being focused on the therapeutic potential of H3 receptor ligands. In this review, Rob Leurs, Patrizio Blandina, Clark Tedford and Henk Timme...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01201-2
更新日期：1998-05-01 00:00:00
abstract：:Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and ch...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2013.12.004
更新日期：2014-03-01 00:00:00
abstract：:Neuromodulin is a neurospecific calmodulin binding protein that is implicated in neurite extension, axonal elongation and long-term potentiation. Yuechueng Liu and Daniel Storm propose that neuromodulin binds and concentrates calmodulin on growth cone membranes and that stimulation of protein kinase C releases high lo...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(90)90195-e
更新日期：1990-03-01 00:00:00
abstract：:During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial ce...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.02.008
更新日期：2016-05-01 00:00:00
abstract：:Alanine-glyoxylate aminotransferase 2 (AGXT2) is a multifunctional mitochondrial aminotransferase that was first identified in 1978. The physiological importance of AGXT2 was largely overlooked for three decades because AGXT2 is less active in glyoxylate metabolism than AGXT1, the enzyme that is deficient in primary h...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.09.005
更新日期：2014-11-01 00:00:00
abstract：:Non-steroidal anti-inflammatory drugs (NSAIDs) have been considered for treatment and prevention of Alzheimer's disease (AD) for more than two decades. Biochemical markers in the brains of individuals with AD suggest that inflammation might be a driving cause of the disease that can be suppressed by drug treatment. In...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.09.004
更新日期：2007-10-01 00:00:00
abstract：:It is generally accepted that muscle wasting is caused by an increase in protein breakdown which seems to be associated with an ATP-dependent, non-lysosomal proteolytic system based on conjugation of proteins to the small polypeptide ubiquitin. Increases in ubiquitin conjugates and in ubiquitin mRNAs are found in the ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(96)10021-3
更新日期：1996-06-01 00:00:00
abstract：:The injectisome type three secretion system (T3SS) is a major virulence factor in Pseudomonas aeruginosa. This bacterium is responsible for severe infections in immunosuppressed or cystic fibrosis patients and has become resistant to many antibiotics. Inhibitors of T3SS may therefore constitute an innovative therapeut...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.05.011
更新日期：2016-09-01 00:00:00
abstract：:Heat shock proteins (HSPs) constitute a large family of proteins involved in protein folding and maturation whose expression is induced by heat shock or other stressors. The major groups are classified based on their molecular weights and include HSP27, HSP40, HSP60, HSP70, HSP90, and large HSPs. HSPs play a significa...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.11.009
更新日期：2017-03-01 00:00:00
abstract：:Three 'alpha 1-adrenoceptors' and three 'alpha 2-adrenoceptors' have now been cloned. How closely do these receptors match the native receptors that have been identified pharmacologically? What are the properties of these receptors, and how do they relate to other members of the cationic amine receptor family? Kevin L...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(91)90499-i
更新日期：1991-02-01 00:00:00
abstract：:Carbonic anhydrase isoform IX (CA IX) is highly overexpressed in many types of cancer. Its expression, which is regulated by the HIF-1 transcription factor, is strongly induced by hypoxia and correlates with a poor response to classical chemo- and radiotherapies. CA IX contributes to acidification of the tumor environ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2006.09.002
更新日期：2006-11-01 00:00:00
abstract：:Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29bp) in mammalian cells has existed for several years. Two recent articles demonstrate that short sequences within long double-stranded (ds)RNAs frequently cause undesirable OTEs in cultured Drosophila cells. These results reveal the...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2007.02.009
更新日期：2007-04-01 00:00:00
abstract：:Recent developments in genetic research using Saccharomyces cerevisiae have provided rapid new methods for identifying the genes that control cellular responses to treatment with a wide variety of agents, including chemicals and radiation. This significantly increases the power of yeast as a model system for studying ...
journal_title：Trends in pharmacological sciences
pub_type： 新闻
doi：10.1016/s0165-6147(02)02082-5
更新日期：2002-10-01 00:00:00
abstract：:Recent studies have proposed a functional link between annexin 1 (ANXA1), an endogenous anti-inflammatory mediator, and receptors of the formyl-peptide family. In particular, exogenous and endogenous ANXA1 and its peptidomimetics interact with one member of this family, the formyl-peptide-receptor-like 1. Further anal...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2003.09.010
更新日期：2003-11-01 00:00:00
abstract：:Antipsychotic drugs (APDs), and the 'atypical' APDs in particular, are commonly associated with metabolic side effects in humans. These include glucose dysregulation, insulin resistance, hyperlipidemia, weight gain and hypertension, which put patients at increased risk of cardiometabolic disorders. The underlying biol...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.07.002
更新日期：2010-10-01 00:00:00
abstract：:It has taken 17 years from the first identification of a voltage-gated Ca2+ channel (CaV) beta-subunit as a band on a gel following purification of skeletal muscle dihydropyridine (DHP) receptors in 1987 to the publication of key information on the structures of Ca2+ channel beta-subunits. Three recent X-ray crystallo...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2004.10.008
更新日期：2004-12-01 00:00:00
abstract：:Snake venom neurotoxins and lymphocyte antigen 6 (Ly6) proteins, most of the latter being membrane tethered by a glycosylphosphatidylinositol (GPI) anchor, have a variety of biological activities, but their three-finger (3F) folding combines them in one Ly6/neurotoxin family. Subsets of two groups, represented by α-ne...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.11.003
更新日期：2015-02-01 00:00:00
abstract：:Therapeutic targeting of the processes that regulate histone modification is a growing area of scientific exploration. Although most interest has concentrated on the various families of enzymes that contribute to these processes, this review focuses on emerging data demonstrating the chemical tractability and therapeu...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2011.12.002
更新日期：2012-03-01 00:00:00
