Abstract：
:Since the first reports on chemokine function, much information has been generated on the implications of these molecules in numerous physiological and pathological processes, as well as on the signaling events activated through their binding to receptors. Despite these extensive studies, no chemokine-related drugs have yet been approved for use in patients with inflammatory or autoimmune diseases. This discrepancy between efforts and results has forced a re-evaluation of the chemokine field. We have explored chemokine receptor conformations at the cell surface and found that, as is the case for other G protein-coupled receptors, chemokine receptors are not isolated entities that are activated following ligand binding; rather, they are found as dimers and/or higher order oligomers at the cell surface, even in the absence of ligands. These complexes form organized arrays that can be modified by receptor expression and ligand levels, indicating that they are dynamic structures. The way in which these receptor complexes are stabilized modulates ligand binding, as well as their pharmacological properties and the signaling events activated. These conformations thus represent a mechanism that increases the broad variety of chemokine functions. Understanding these receptor interactions and their dynamics at the cell surface is thus critical for influencing chemokine function and could open up new possibilities for drug design.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Muñoz LM,Lucas P,Holgado BL,Barroso R,Vega B,Rodríguez-Frade JM,Mellado Mdoi
10.1016/j.pharmthera.2011.05.002subject
Has Abstractpub_date
2011-09-01 00:00:00pages
351-8issue
3eissn
0163-7258issn
1879-016Xpii
S0163-7258(11)00102-1journal_volume
131pub_type
杂志文章,评审abstract：:The vascular endothelium not only is a single monolayer of cells between the vessel lumen and the intimal wall, but also plays an important role by controlling vascular function and structure mainly via the production of nitric oxide (NO). The so called "cardiovascular risk factors" are associated with endothelial dys...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.06.003
更新日期：2014-12-01 00:00:00
abstract：:Nucleoside monophosphate kinases catalyze the reversible phosphotransferase reaction between nucleoside triphosphates and monophosphates, i.e., monophosphates are converted to their corresponding diphosphate form. These enzymes play an important role in the synthesis of nucleotides that are required for a variety of c...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(00)00048-6
更新日期：2000-08-01 00:00:00
abstract：:Common arrhythmias, particularly atrial fibrillation (AF) and ventricular tachycardia/fibrillation (VT/VF) are a major public health concern. Classic antiarrhythmic (AA) drugs for AF are of limited effectiveness, and pose the risk of life-threatening VT/VF. For VT/VF, implantable cardiac defibrillators appear to be th...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.03.003
更新日期：2011-11-01 00:00:00
abstract：:The past three decades have witnessed a welcome expansion of the therapeutic armamentarium for the management of pulmonary arterial hypertension (PAH). However, against this backdrop, there have been some notable disappointments in drug development. Here we use these as case studies to emphasize the importance of info...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.04.012
更新日期：2016-08-01 00:00:00
abstract：:Decades of research have established that the biological functions of thyrotropin-releasing hormone (TRH) extend far beyond its role as a regulator of the hypothalamic-pituitary-thyroid axis. Gary et al. [Gary, K.A., Sevarino, K.A., Yarbrough, G.G., Prange, A.J. Jr., Winokur, A. (2003). The thyrotropin-releasing hormo...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.09.004
更新日期：2009-01-01 00:00:00
abstract：:Substantial progress in the identification of genes encoding for a large number of proteins responsible for various aspects of neurotransmitter release, postsynaptic detection and downstream signaling, has advanced our understanding of the mechanisms by which neurons communicate and interact. Nicotinic acetylcholine r...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.08.012
更新日期：2013-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90008-6
更新日期：1994-04-01 00:00:00
abstract：:The understanding of renal fibrosis in chronic kidney disease (CKD) remains as a challenge. More than 10% of the population of developed countries suffer from CKD. Proliferation and activation of myofibroblasts and accumulation of extracellular matrix proteins are the main features of kidney fibrosis, a process in whi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.10.003
更新日期：2015-12-01 00:00:00
abstract：:Known treatments of type 2 diabetes mellitus have limitations such as weight gain, and hypoglycaemias. A new perspective is the use of incretin hormones and incretin enhancers. Incretins are defined as being responsible for the higher insulin release after an oral glucose load compared to an intravenous glucose load. ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.06.002
更新日期：2009-10-01 00:00:00
abstract：:In the last decade, there have been considerable advances in the understanding of the pathophysiology of malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Over 80% of SCD occurs in patients with organic heart disease. However, approximately 10%-15% of SCD occurs in the presence of structurall...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.09.002
更新日期：2015-11-01 00:00:00
abstract：:This review concerns the development of small molecule therapeutics for the inherited neurodegenerative disease Friedreich ataxia (FRDA). FRDA is caused by transcriptional repression of the nuclear FXN gene, encoding the essential mitochondrial protein frataxin and accompanying loss of frataxin protein. Frataxin insuf...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.06.014
更新日期：2007-11-01 00:00:00
abstract：:Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors family. PPARs are a family of 3 ligand-activated transcription factors: PPARalpha (NR1C1), PPARbeta/delta (NUC1; NR1C2), and PPARgamma (NR1C3). PPARalpha, -beta/delta, and -gamma are encoded by different genes but show sub...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.08.007
更新日期：2006-06-01 00:00:00
abstract：:Since its commercial advent in 1985, transcranial magnetic stimulation (TMS), a technique for stimulating neurons in the cerebral cortex through the scalp, safely and with minimal discomfort, has captured the imaginations of scientists, clinicians and lay observers. Initially a laboratory tool for neurophysiologists s...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.09.003
更新日期：2012-01-01 00:00:00
abstract：:Binge-eating disorder (BED) is the most prevalent eating disorder with estimates of 2-5% of the general adult population. Nonetheless, its pathophysiology is poorly understood. Furthermore, there exist few therapeutic options for its effective treatment. Here we review the current state of binge-eating neurobiology an...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.08.002
更新日期：2018-02-01 00:00:00
abstract：:Metabolic diseases have a tremendous impact on human morbidity and mortality. Numerous targets regulating adenosine monophosphate kinase (AMPK) have been identified for treating the metabolic syndrome (MetS), and many compounds are being used or developed to increase AMPK activity. In parallel, the cyclic nucleotide p...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107475
更新日期：2020-04-01 00:00:00
abstract：:In the heart, Ca(2+) released from the intracellular Ca(2+) storage site, the sarcoplasmic reticulum (SR), is the principal determinant of cardiac contractility. SR Ca(2+) release is controlled by dedicated molecular machinery, composed of the cardiac ryanodine receptor (RyR2) and a number of accessory proteins, inclu...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.06.002
更新日期：2008-09-01 00:00:00
abstract：:Statins are effective drugs to reduce cardiovascular events secondary to dyslipidemia; however, they cause frequent undesirable side effects. The incidence of statin-induced myotoxicity (SIM) is presented by 7 to 29% of patients, depending upon the report. SIM may develop in presence of abnormally high concentrations ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.02.029
更新日期：2017-07-01 00:00:00
abstract：:The chewing of the stimulant leaf khat is a habit that is widespread in certain countries of East Africa and the Arabian peninsula. During the last decade, important progress has been made in understanding the pharmacological basis for the effects of khat. It is now known that the CNS action of this drug is due to the...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90057-9
更新日期：1990-01-01 00:00:00
abstract：:The thyroid hormone (TH; 3,3',5,5'-tetra-iodothyronine and 3,3',5'-triiodothyronine) regulates growth, development, and critical metabolic functions. Thyroid diseases are among the most prevalent group of metabolic disorders in the Western world. TH exerts effects through complex biological pathways, which offer a wea...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00219-x
更新日期：2002-06-01 00:00:00
abstract：:This review focuses on microRNAs (miRs) in cardiac surgery, where they are emerging as potential targets for therapeutic intervention as well as novel clinical biomarkers. Identification of the up/down-regulation of specific miRs in defined groups of cardiac surgery patients can lead to the development of novel strate...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.11.004
更新日期：2017-02-01 00:00:00
abstract：:Proteolytic degradation of unwanted proteins by the ubiquitin-proteasome system (UPS) is critical for normal maintenance of various cellular functions. Parkinson's disease (PD), one of the most prevalent neurodegenerative disorders, is characterized by prominent and irreversible nigral dopaminergic neuronal loss and i...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.04.001
更新日期：2007-06-01 00:00:00
abstract：:The developing lung is highly susceptible to damage from exposure to environmental toxicants particularly due to the protracted maturation of the respiratory system, extending from the embryonic phase of development in utero through to adolescence. The functional organization of the lungs requires a coordinated ontoge...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.01.011
更新日期：2007-05-01 00:00:00
abstract：:Artemisinins are a unique class of antimalarial drugs with significant potential for drug repurposing for a wide range of diseases including cancer. Cancer is a leading cause of death globally and the majority of cancer related deaths occur in Low and Middle Income Countries (LMICs) where conventional treatment option...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107706
更新日期：2020-12-01 00:00:00
abstract：:Asthma is a chronic disorder characterized by persistent inflammation of the airways with mucosal infiltration of eosinophils, T lymphocytes, and mast cells, and release of proinflammatory cytokines and lipid mediators. The natural resolution of airway inflammation is now recognized as an active host response, with hi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.01.004
更新日期：2018-06-01 00:00:00
abstract：:Nitric oxide (NO) exerts a variety of biological actions under both physiological and pathological conditions. NO is synthesized by three distinct NO synthase (NOS) isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS), all of which are expressed in the human cardiovascular system. The role...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.08.010
更新日期：2010-12-01 00:00:00
abstract：:The cardiovascular system is highly organised in time; blood pressure (BP), heart rate (HR), peripheral resistance, pressure and the release/activity of vasodilating hormones all display pronounced circadian variations. Pathophysiological events within the cardiovascular system are also not random, as shown for instan...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.11.008
更新日期：2006-09-01 00:00:00
abstract：:During physiological development and after a stressor event, vascular cells communicate with each other to evoke new vessel formation-a process known as angiogenesis. This communication occurs via direct contact and via paracrine release of proteins and nucleic acids, both in a free form or encapsulated into micro-ves...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.10.001
更新日期：2017-03-01 00:00:00
abstract：:The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90-kDa heat-shock protein, hsp90 and the 94-kDa glucose-regulated protein, grp94, major molecular chaperones of the cytosol and of the endoplasmic reticulum, respectively) has become an increasingly active subject of research in the past...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00013-8
更新日期：1998-08-01 00:00:00
abstract：:Neurosteroids are neuroactive brain-born steroids. They can act through non-genomic and/or through genomic pathways. Genomic pathways are largely described for steroid hormones: the binding to nuclear receptors leads to transcription regulation. Pregnenolone, Dehydroepiandrosterone, their respective sulfate esters and...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.06.011
更新日期：2018-11-01 00:00:00
abstract：:Activation of receptors coupled to inhibitory G proteins (Galpha i/o) has opposing consequences for cyclic AMP accumulation and the activity of cyclic AMP-dependent protein kinase, depending on the duration of stimulation. Acute activation inhibits the activity of adenylate cyclase, thereby attenuating cyclic AMP accu...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.12.005
更新日期：2005-06-01 00:00:00
