GPCR deorphanizations: the novel, the known and the unexpected transmitters.

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

authors： Leurs R,Blandina P,Tedford C,Timmerman H

更新日期：1998-05-01 00:00:00

abstract：:Oxidative stress is a key pathologic factor in neurodegenerative diseases such as Alzheimer and Parkinson diseases (AD, PD). The failure of free-radical-scavenging antioxidants in clinical trials pinpoints an urgent need to identify and to block major sources of oxidative stress in neurodegenerative diseases. As a maj...

journal_title：Trends in pharmacological sciences

authors： Gao HM,Zhou H,Hong JS

更新日期：2012-06-01 00:00:00

abstract：:The use of genetically-engineered mice has identified alpha2- and alpha3-subunit containing GABA(A) receptors as principal contributors to the spinal disinhibition that occurs after inflammation and neuropathic injury. Pharmacological comparison of subtype selective allosteric modulators such as NS11394 and L838417 wi...

journal_title：Trends in pharmacological sciences

authors： Munro G,Ahring PK,Mirza NR

更新日期：2009-09-01 00:00:00

abstract：:Disorders of the central nervous system (CNS) have many etiologies compounded by limited options for treatment. The lack of successful treatments for these disorders stems from the difficulty of gaining effective access to the CNS through the blood-brain barrier, and the irreplaceable nature of neurons. Here, we revie...

journal_title：Trends in pharmacological sciences

authors： Valente LA,Begg LR,Filiano AJ

更新日期：2019-07-01 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

authors： Boyda HN,Tse L,Procyshyn RM,Honer WG,Barr AM

更新日期：2010-10-01 00:00:00

abstract：:Erythropoietin (EPO) has emerged as a versatile growth factor that has transcended its traditional role as a mediator of erythroid maturation to one that modulates stem cell development, cellular protection and angiogenesis in the brain. As a possible candidate for nervous system disorders, it becomes crucial to under...

journal_title：Trends in pharmacological sciences

authors： Maiese K,Li F,Chong ZZ

更新日期：2004-11-01 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

authors： McCarthy SA,Kuzu I,Gatter KC,Bicknell R

更新日期：1991-12-01 00:00:00

abstract：:Progress in understanding the genetic changes that drive tumorigenesis has enabled the development of molecularly targeted anticancer therapy. The first small molecule targeted to a specific protein was imatinib mesylate (Gleevec, STI571), which is used to treat chronic myeloid leukemia (CML). A recent article present...

journal_title：Trends in pharmacological sciences

authors： Michor F

更新日期：2007-05-01 00:00:00

abstract：:Drugs that cause liver injury often 'stress' mitochondria and activate signal transduction pathways important in determining cell survival or death. In most cases, hepatocytes adapt to the drug-induced stress by activating adaptive signaling pathways, such as mitochondrial adaptive responses and nuclear factor erythro...

journal_title：Trends in pharmacological sciences

authors： Han D,Dara L,Win S,Than TA,Yuan L,Abbasi SQ,Liu ZX,Kaplowitz N

更新日期：2013-04-01 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：:Chronic obstructive pulmonary disease (COPD) is caused mostly by cigarette smoking but its specific molecular mechanisms are obscure. Current theories suggest that the inflammation and oxidative stress induced by smoking lead to proteolytic imbalance and progressive lung structural derangement, with disease susceptibi...

journal_title：Trends in pharmacological sciences

authors： Anderson GP,Bozinovski S

更新日期：2003-02-01 00:00:00

abstract：:Release of cytotoxic granule proteins from activated eosinophil granules is considered to be a key pathogenic mechanism in eosinophilic diseases. Degenerated eosinophils and extracellular eosinophil granules have been repeatedly depicted. The present overview describes evidence that eosinophil lysis and distribution o...

journal_title：Trends in pharmacological sciences

authors： Persson CG,Erjefält JS

更新日期：1997-04-01 00:00:00

abstract：:There is increasing awareness of the compartmentalization of cAMP signalling--the means by which cAMP levels change in discrete domains of the cell with discrete local consequences. Current developments in understanding the organization of adenylyl cyclases in the plasma membrane are illuminating how the earliest part...

journal_title：Trends in pharmacological sciences

authors： Cooper DM,Crossthwaite AJ

更新日期：2006-08-01 00:00:00

abstract：:Cytochrome P450 3A (CYP3A) enzymes metabolize a wide variety of xenobiotics including many drugs. Because CYP3A is localized in both the liver and intestine, it can make a major contribution to the presystemic elimination of substrate drugs after oral administration ('first-pass metabolism'). However, assessments of t...

journal_title：Trends in pharmacological sciences

authors： van Herwaarden AE,van Waterschoot RA,Schinkel AH

更新日期：2009-05-01 00:00:00

abstract：:Seven-transmembrane receptors are prototypic allosteric proteins with the ability to adopt numerous conformations, many of which interact with cellular partners to initiate cellular biochemical processes. Defining efficacy as the ability of ligands to stabilize some of these conformations (which, in turn, possess phys...

journal_title：Trends in pharmacological sciences

authors： Kenakin T

更新日期：2007-08-01 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：:The breast cancer resistance protein [BCRP (also known as ABCG2)] belongs to the ATP binding cassette (ABC) family of transmembrane drug transporters. BCRP has a broad substrate specificity and actively extrudes a wide variety of drugs, carcinogens and dietary toxins from cells. Situated in the apical plasma membrane ...

journal_title：Trends in pharmacological sciences

authors： van Herwaarden AE,Schinkel AH

更新日期：2006-01-01 00:00:00

abstract：:The imbalance theory proposes that arterial thrombosis is dependent on a ratio or balance between the cyclooxygenase (COX)-1-dependent generation of thromboxane in platelets and the COX-2-dependent generation of prostacyclin in the endothelium. Accordingly, by reducing endothelium-derived prostacyclin levels, selectiv...

journal_title：Trends in pharmacological sciences

authors： Flavahan NA

更新日期：2007-03-01 00:00:00

abstract：:Pharmacology as a modern science was introduced in China approximately 150 years ago, and has been used since then to study traditional Chinese medicine (TCM). Pharmacology has experienced its own development over this time and continues to provide new tools for the study of TCM. In the present review, three models fo...

journal_title：Trends in pharmacological sciences

authors： Liu X,Wu WY,Jiang BH,Yang M,Guo DA

更新日期：2013-11-01 00:00:00

abstract：:The concept that receptors can exist in multiple conformational states is becoming a physical reality. A fundamental question is how many active states need to be proposed in order to account for pharmacological observations, in particular, the finding that the same receptor type can exhibit a different agonist pharma...

journal_title：Trends in pharmacological sciences

authors： Leff P,Scaramellini C,Law C,McKechnie K

更新日期：1997-10-01 00:00:00

abstract：:K(+) channels are macromolecules embedded in biological membranes, where they play a key role in cellular excitability and signal transduction pathways. Knowledge of their structure should help improve our understanding of their function and lead to the design of therapeutic compounds. Most pharmacological and structu...

journal_title：Trends in pharmacological sciences

authors： Rodríguez de la Vega RC,Merino E,Becerril B,Possani LD

更新日期：2003-05-01 00:00:00

abstract：:The phospholipase A2 enzymes are important components of the cellular machinery that responds to inflammatory stimuli and maintains cell homeostasis by membrane remodelling. Their role as the rate-limiting step in the production of pro-inflammatory lipid mediators makes these enzymes an important therapeutic target fo...

journal_title：Trends in pharmacological sciences

authors： Glaser KB,Mobilio D,Chang JY,Senko N

更新日期：1993-03-01 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

authors： Game JC

更新日期：2002-10-01 00:00:00

abstract：:Much regarding the engagement of the G(12) family of heterotrimeric G proteins (G(12) and G(13)) by agonist-activated receptors remains unclear. For example, the identity of receptors that couple unequivocally to G(12) and G(13) and how signals are allocated among these and other G proteins remain open questions. Part...

journal_title：Trends in pharmacological sciences

authors： Riobo NA,Manning DR

更新日期：2005-03-01 00:00:00

abstract：:B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a br...

journal_title：Trends in pharmacological sciences

authors： John P,Wei Y,Liu W,Du M,Guan F,Zang X

更新日期：2019-11-01 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

authors： Prinjha RK,Witherington J,Lee K

更新日期：2012-03-01 00:00:00

abstract：:Current medicines for the clinical management of inflammatory diseases act by inhibiting specific enzymes or antagonising specific receptors or blocking their ligands. In the past decade, a new paradigm in our understanding of the inflammatory process has emerged with the appreciation of genetic, molecular, and cellul...

journal_title：Trends in pharmacological sciences

authors： Perretti M,Leroy X,Bland EJ,Montero-Melendez T

更新日期：2015-11-01 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：:Opioid receptors are expressed on peripheral sensory nerve endings, cutaneous cells, and immune cells; and local application of opioids is used for the treatment of inflammatory pain in arthritis, burns, skin grafts, and chronic wounds. However, peripherally active opioids can also directly modulate the inflammatory p...

journal_title：Trends in pharmacological sciences

authors： Stein C,Küchler S

更新日期：2013-06-01 00:00:00

abstract：:Due to its negative chronotropic and inotropic effects, adenosine has to date been considered as a cardiodepressant agent. However, adenosine increases ventricular automaticity. This review by Jesus Hernández and Alexandre Ribeiro discusses the experimental and clinical evidence for the excitatory effects of adenosine...

journal_title：Trends in pharmacological sciences

authors： Hernández J,Ribeiro JA

更新日期：1996-04-01 00:00:00