Abstract:
:Controversy over the meaning of pharmacological parameters often arises because of a lack of appreciation of different hierarchical levels of analysis. In a recent letter in Trends in Pharmacological Sciences, Zhang and Kavana [1] concluded that my two-state model for allosterism lacks cooperativity, even though Figures 5 and 6 in my review [2] illustrate examples of how the two-state model yields specific cooperativity values. Here, I explain how the two-state model (receptor-state analysis) gives rise to the cooperativity parameter (α) of the allosteric ternary complex model (receptor-population analysis).
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Ehlert FJdoi
10.1016/j.tips.2016.06.001subject
Has Abstractpub_date
2016-08-01 00:00:00pages
620-623issue
8eissn
0165-6147issn
1873-3735pii
S0165-6147(16)30056-6journal_volume
37pub_type
评论,信件abstract::Over the past few decades, mortality resulting from cardiovascular disease (CVD) steadily decreased in western countries; however, in recent years, the decline has become offset by the increase in obesity. Obesity is strongly associated with the metabolic syndrome and its atherogenic dyslipidemia resulting from insuli...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.04.010
更新日期:2015-06-01 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::5-Hydroxytryptamine (5-HT), dopamine and norepinephrine are important monoamine neurotransmitters implicated in multiple brain mechanisms and regulated by high-affinity transmembrane monoamine transporters. Although knockout mice lacking 5-HT, dopamine or norepinephrine transporters are widely used to assess brain mon...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.01.002
更新日期:2007-03-01 00:00:00
abstract::Classical targeted drug discovery is based on targeting druggable targets, typically kinases and receptors of which the function can be agonized or antagonized. This strategy meets difficulties in cases such as Huntington's disease (HD) and similar neurodegenerative disorders, where the pathological function of the pr...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.12.001
更新日期:2014-02-01 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::Neuronal Ca2+-sensor (NCS) proteins constitute a subfamily of closely related EF-hand Ca2+-binding proteins that are expressed mainly in neurons or retinal photoreceptor cells. A variety of different neuronal functions have been attributed to these proteins. However, important new discoveries indicate that these prote...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.04.008
更新日期:2005-07-01 00:00:00
abstract::HIV-1 integrase (IN) executes the insertion of proviral DNA into the host cell genome, an essential step in the retroviral life cycle. This is a multi-step process that starts in the cytosol and culminates in the nucleus of the infected cell. It is becoming increasingly clear that IN interacts with a wide range of dif...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.09.005
更新日期:2007-10-01 00:00:00
abstract::Centrally acting drugs interfere with the function of central neurotransmitter systems. This often requires intact neuronal connections and is therefore best studied in vivo. Here, Gaetano Di Chiara describes the technique of brain dialysis, which permits direct in-vivo sampling of neurotransmitters and their metaboli...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(90)90197-g
更新日期:1990-03-01 00:00:00
abstract::cGMP inhibits hypertrophy, decreases fibrosis, and protects against cardiac ischemia-reperfusion (I/R) injury. Gene-targeting studies have not defined a clear role for its major downstream effector, cGMP-dependent protein kinase I (cGKI), in cardiac hypertrophy, but do implicate cGMP-cGKI signaling in fibrosis and I/R...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2014.05.003
更新日期:2014-08-01 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::Although an established regulator of many cellular functions, the phosphoinositide phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2) appears to have evaded the attention of drug-discovery companies. An increasing number of reports have identified potential links between PtdIns(4,5)P2-mediated signalling pathways...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.10.004
更新日期:2005-12-01 00:00:00
abstract::Clinical implementation of two recently approved antisense RNA therapeutics - Exondys51® to treat Duchenne muscular dystrophy (Duchenne MD) and Spinraza® as a treatment for spinal muscular atrophy (SMA) - highlights the therapeutic potential of antisense oligonucleotides (ASOs). As shown in the Duchenne and Becker cas...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.09.001
更新日期:2018-11-01 00:00:00
abstract::Exposing the heart to brief episodes of ischaemia protects the myocardium and vascular endothelial cells against functional damage and cell death caused by subsequent prolonged ischaemia. Elucidation of the mechanisms that are involved in this phenomenon known as 'ischaemic preconditioning' and identification of drugs...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01483-8
更新日期:2000-06-01 00:00:00
abstract::Annexin A1 (ANXA1) is an endogenous protein known to have potent anti-inflammatory properties in the peripheral system. It has also been detected in the brain, but its function there is still ambiguous. In this review, we have, for the first time, collated the evidence currently available on the function of ANXA1 in t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.12.003
更新日期:2008-03-01 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::Glucocorticosteroids are highly effective in controlling inflammation and the molecular mechanisms involved are now becoming clear. Activation of glucocorticoid receptors results in increased or decreased transcription of a number of genes involved in the inflammatory process. Of particular importance is the repressio...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(93)90184-l
更新日期:1993-12-01 00:00:00
abstract::In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.02.008
更新日期:2015-05-01 00:00:00
abstract::The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of immunomodulatory receptors whose functions are regulated by their glycan ligands. Siglecs are attractive therapeutic targets because of their cell type-specific expression pattern, endocytic properties, high expression on certain lymphomas/l...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.06.008
更新日期:2015-10-01 00:00:00
abstract::Cannabis (marijuana) is not only a frequently abused drug but also has the potential for the development of useful agents for the treatment of emesis, anorexia and multiple sclerosis. In this article, the effects of modulation of transmitter release by cannabinoids in both the CNS and the PNS of various species, inclu...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01805-8
更新日期:2001-11-01 00:00:00
abstract::Recruitment of leukocytes either during development or to the site of injury is crucial. The molecular regulation of cell trafficking is complex but well orchestrated by the temporal and spatial expression of a multitude of chemokines (chemoattractant cytokines) and chemokine receptors. The chemokines, classified prim...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(99)01342-5
更新日期:1999-04-01 00:00:00
abstract::Addiction biology has focused on the mechanisms of the positive and negative reinforcing actions of addictive drugs but neglected potential benefits. Two new studies provide the first insights into a neurobiology of psychoactive drug instrumentalization. This may help us design better models for addiction neuroscience...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2017.03.005
更新日期:2017-06-01 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::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::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::Inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease (PR) are widely used in the clinical treatment of AIDS. However, the emergence of drug-resistant variants of HIV-1 severely limits the long-term effectiveness of these drugs. In this review, the molecular basis of resista...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(02)02054-0
更新日期:2002-08-01 00:00:00
abstract::Parkinson's disease (PD) is a progressive neurodegenerative disorder. Although therapies that treat the symptoms of the disease have proven efficacy, strategies that slow or stop the neurodegenerative process are currently not available. Recently, the National Institute of Neurological Disorders and Stroke (NINDS) con...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2004.03.003
更新日期:2004-05-01 00:00:00
abstract::Insect nicotinic acetylcholine (nACh) receptors are molecular targets of insecticides such as neonicotinoids that are used to control disease-carrying insects and agricultural pests. To date, several insect nACh receptor subunits have been identified, indicating different nACh receptor subtypes and pharmacological pro...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.11.006
更新日期:2007-01-01 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::The melanocortin receptors are a subfamily of G-protein-coupled, rhodopsin-like receptors that are rapidly being acknowledged as an extremely promising target for pharmacological intervention in a variety of different inflammatory pathologies, including stroke. Stroke continues to be a leading cause of death worldwide...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2010.11.010
更新日期:2011-02-01 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