Protein engineering and the study of structure--function relationships in receptors.

abstract：:Several clinical studies document a greater discrimination between asthmatic and healthy subjects in bronchial responsiveness to a range of stimuli such as cold air, distilled water and sodium metabisulphite, than to conventional bronchoconstrictor agonists including histamine and methacholine. One of the mechanisms t...

journal_title：Trends in pharmacological sciences

authors： Spina D,Shah S,Harrison S

更新日期：1998-11-01 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

authors： Schulte G,Wright SC

更新日期：2018-09-01 00:00:00

abstract：:The rise of multidrug-resistant pathogens and the dearth of new antibiotic development place an existential strain on successful infectious disease therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health catastrophe. Reconceptualizing antibiotic t...

journal_title：Trends in pharmacological sciences

authors： Munguia J,Nizet V

更新日期：2017-05-01 00:00:00

abstract：:As we have learnt from earlier articles in our series on the pharmacology of excitatory amino acids, neurons and glia express several subtypes of excitatory amino acid receptor, the activation of which increases intracellular free calcium ion concentration. In this sixth article, Mark Mayer and Richard Miller detail t...

journal_title：Trends in pharmacological sciences

authors： Mayer ML,Miller RJ

更新日期：1990-06-01 00:00:00

abstract：:It has been over 50years since Sir James Black developed the first beta adrenergic receptor (βAR) blocker to treat heart disease. At that time, the concept of cell surface receptors was relatively new and not widely accepted, and most of the tools currently used to characterize plasma membrane receptors had not been d...

journal_title：Trends in pharmacological sciences

authors： Kobilka BK

更新日期：2011-04-01 00:00:00

abstract：:The hypothalamic neuropeptide oxytocin (OT) has attracted the attention both of the scientific community and a general audience because of its prosocial effects in mammals, and OT is now seen as a facilitator of mammalian species propagation. Furthermore, OT is a candidate for the treatment of social deficits in sever...

journal_title：Trends in pharmacological sciences

authors： Chini B,Verhage M,Grinevich V

更新日期：2017-11-01 00:00:00

abstract：:Cytochromes P450 are a superfamily of haem-containing monooxygenases. In mammals, two general classes of P450s exist: six families involved in steroid and bile acid biosynthetic pathways of metabolism; four families containing numerous individual P450s, mainly responsible for metabolism of foreign compounds. Many of t...

journal_title：Trends in pharmacological sciences

authors： Gonzalez FJ

更新日期：1992-09-01 00:00:00

abstract：:In the past 20 years we have learned a great deal about GABAA receptor (GABAAR) subtypes, and which behaviors are regulated or which drug effects are mediated by each subtype. However, the question of where GABAARs involved in specific drug effects and behaviors are located in the brain remains largely unanswered. We ...

journal_title：Trends in pharmacological sciences

authors： Engin E,Benham RS,Rudolph U

更新日期：2018-08-01 00:00:00

abstract：:Inappropriate production of the iron-regulatory hormone hepcidin contributes to the pathogenesis of common iron disorders. Absolute or relative deficiency of hepcidin causes iron overload in hereditary hemochromatosis and iron-loading anemias. Elevated hepcidin causes iron restriction in inflammatory conditions includ...

journal_title：Trends in pharmacological sciences

authors： Ruchala P,Nemeth E

更新日期：2014-03-01 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

authors： Di Chiara G

更新日期：1990-03-01 00:00:00

abstract：:Lithium is the simplest therapeutic agent available for the treatment of depression and has been used for over 100 years, yet no definitive mechanism for its effect has been established. Among the proposed mechanisms, two lithium-sensitive signal transduction pathways are active in the brain; these are mediated by gly...

journal_title：Trends in pharmacological sciences

authors： Williams RS,Harwood AJ

更新日期：2000-02-01 00:00:00

abstract：:The 5-HT7 receptor was among a group of 5-HT receptors that were discovered using targeted cloning strategies 12 years ago. This receptor is a seven-transmembrane-domain G-protein-coupled receptor that is positively linked to adenylyl cyclase. The distributions of 5-HT7 receptor mRNA, immunolabeling and radioligand bi...

journal_title：Trends in pharmacological sciences

authors： Hedlund PB,Sutcliffe JG

更新日期：2004-09-01 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

authors： Tsetlin VI

更新日期：2015-02-01 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

authors： Rodionov RN,Jarzebska N,Weiss N,Lentz SR

更新日期：2014-11-01 00:00:00

abstract：:Receptors, enzymes, and ion channels are traditional targets of therapeutic development. A common strategy is to target these proteins with agents that either activate or suppress their activity with ligands or substrates that occupy orthosteric sites or have allosteric interactions. An alternative approach involves r...

journal_title：Trends in pharmacological sciences

authors： Conn PM,Spicer TP,Scampavia L,Janovick JA

更新日期：2015-08-01 00:00:00

abstract：:Pairing orphan G-protein-coupled receptors (GPCRs) to potential ligands found in tissue extracts or in libraries of synthetic compounds has identified an ever-increasing number of transmitters, some of which are novel, some of which were previously known and, more recently, some of which are unexpected. These discover...

journal_title：Trends in pharmacological sciences

authors： Civelli O

更新日期：2005-01-01 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

authors： Richards MW,Butcher AJ,Dolphin AC

更新日期：2004-12-01 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

authors： Liu YC,Storm DR

更新日期：1990-03-01 00:00:00

abstract：:Exposure of cells to agonists of receptors linked to G proteins can result in downregulation of cellular levels or redistribution of G proteins from membranes to the cytosol. Agonist-induced reductions in G protein levels have been observed for members of each of the Gs, Gi and Gq families of G proteins, are likely to...

journal_title：Trends in pharmacological sciences

authors： Milligan G

更新日期：1993-11-01 00:00:00

abstract：:Pathogenic granulocytes (eosinophils and neutrophils) infiltrate airway tissues in asthma and chronic obstructive pulmonary disease. Granulocytes release tissue-toxic and inflammatory mediators, making their removal an important pharmacological goal. Removal is thought to be accomplished through apoptosis followed by ...

journal_title：Trends in pharmacological sciences

authors： Uller L,Persson CG,Erjefält JS

更新日期：2006-09-01 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

authors： Al-Mawsawi LQ,Neamati N

更新日期：2007-10-01 00:00:00

abstract：:The British Pharmacological Society (BPS) is currently celebrating its 75th anniversary. It is therefore a young society compared with some other biomedical societies and particularly when compared with the origins of the oldest learned societies. In this article, I briefly review the origins of learned societies and ...

journal_title：Trends in pharmacological sciences

authors： Green AR

更新日期：2006-03-01 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

authors： Kalueff AV,Ren-Patterson RF,Murphy DL

更新日期：2007-03-01 00:00:00

abstract：:Hypertension is prevalent and affects approximately 1 in every 4 adults in the Western world. Although many drugs are effective in treating hypertension, an individual's response to treatment is unpredictable. Pharmacogenetics holds the promise of becoming a tool to predict this response but obstacles and shortcomings...

journal_title：Trends in pharmacological sciences

authors： Kurland L,Lind L,Melhus H

更新日期：2005-09-01 00:00:00

abstract：:Enveloped viruses pose an important health threat because most of the persistent and many emerging viruses are enveloped. In particular, newly emerging viruses create a need to develop broad-spectrum antivirals, which usually are obtained by targeting host cell factors. Persistent viruses have developed efficient stra...

journal_title：Trends in pharmacological sciences

authors： Wisskirchen K,Lucifora J,Michler T,Protzer U

更新日期：2014-09-01 00:00:00

abstract：:Until recently, release studies have failed to indicate the existence of autoreceptors on motor nerves. Ignaz Wessler now reports on a refinement of the technique - the measurement of newly synthesized [3H]acetylcholine released from the phrenic nerve - which provides clear evidence in support of release-modulating au...

journal_title：Trends in pharmacological sciences

authors： Wessler I

更新日期：1989-03-01 00:00:00

abstract：:Nearly all molecules known to signal cells via G proteins have been assigned a cloned G-protein-coupled-receptor (GPCR) gene. This has been the result of a decade-long genetic search that has also identified some receptors for which ligands are unknown; these receptors are described as orphans (oGPCRs). More than 80 o...

journal_title：Trends in pharmacological sciences

authors： Marchese A,George SR,Kolakowski LF Jr,Lynch KR,O'Dowd BF

更新日期：1999-09-01 00:00:00

abstract：:Cyclic AMP (cAMP) steers the generation of basal heart beat in the sinoatrial node. It also induces sinoatrial tachycardia and increased cardiac force, elicited through activation of Gs-protein-coupled receptors (GsPCRs). Phosphodiesterases (PDEs) hydrolyse cAMP. In the heart mainly PDE3 and PDE4 would be expected to ...

journal_title：Trends in pharmacological sciences

authors： Kaumann AJ

更新日期：2011-07-01 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

authors： Fukata Y,Amano M,Kaibuchi K

更新日期：2001-01-01 00:00:00

abstract：:There is a variety of pressures on pharmacology teachers to replace real laboratory practicals with simulations but do they help students achieve the required learning objectives? In this article, the marks obtained by students in a variety of assessments using 'wet' or simulated practicals are analysed. Poorer perfor...

journal_title：Trends in pharmacological sciences

authors： Hughes IE

更新日期：2001-02-01 00:00:00