Roles of CRAC and Cav-like channels in T cells: more than one gatekeeper?


:Ca2+ channels in the plasma membrane of T cells vitally influence Ca2+-dependent signals that lead ultimately to cytokine secretion, cellular proliferation and apoptosis. Conventional models depict the Ca2+ inrush across the T-cell membrane following T-cell receptor engagement as being due to Ca2+-release-activated Ca2+ (CRAC) channels. A poorly understood mechanism detects the lowered Ca2+ concentrations within intracellular stores that open CRAC channels. Mammalian homologs of the Drosophila transient receptor potential Ca2+ channels possibly help to gate the store-operated, Ca2+-borne CRAC current. In this article, we review evidence of a supplementary involvement of other Ca2+ channels, the opening of which does not necessarily reflect intracellular Ca2+-store depletion. We highlight a role for variants of L-type voltage-dependent Ca2+ channels in increasing intracellular Ca2+ concentrations during activation. For more-accurate modeling of lymphocyte activation and possible pharmacological interventions, future research should aim to identify physiologically relevant situations in which such channels help to shape the Ca2+ signal.


Trends Pharmacol Sci


Kotturi MF,Hunt SV,Jefferies WA




Has Abstract


2006-07-01 00:00:00














  • New genome-wide methods bring more power to yeast as a model organism.

    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


    authors: Game JC

    更新日期:2002-10-01 00:00:00

  • Novel GPCRs and their endogenous ligands: expanding the boundaries of physiology and pharmacology.

    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

    pub_type: 杂志文章,评审


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

    更新日期:1999-09-01 00:00:00

  • Your bleeding heart: lessons from low tissue factor expression in mice.

    abstract::Tissue factor (TF) is the cellular receptor and cofactor for blood coagulation factor VII (FVII). Exposure of flowing blood to cells that express TF leads to the initiation of blood coagulation. A recent study of mice expressing low levels of TF has demonstrated the importance of TF and FVII in maintaining adequate ha...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: McVey JH

    更新日期:2003-06-01 00:00:00

  • Human Brain Neuropharmacology: A Platform for Translational Neuroscience.

    abstract::Central nervous system (CNS) drug development has been plagued by a failure to translate effective therapies from the lab to the clinic. There are many potential reasons for this, including poor understanding of brain pharmacokinetic (PK) and pharmacodynamic (PD) factors, preclinical study flaws, clinical trial design...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Dragunow M

    更新日期:2020-11-01 00:00:00

  • Prostaglandins and chronic inflammation.

    abstract::Chronic inflammation is the basis of various chronic illnesses including cancer and vascular diseases. However, much has yet to be learned how inflammation becomes chronic. Prostaglandins (PGs) are well established as mediators of acute inflammation, and recent studies in experimental animals have provided evidence th...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Aoki T,Narumiya S

    更新日期:2012-06-01 00:00:00

  • Siglecs as targets for therapy in immune-cell-mediated disease.

    abstract::The sialic-acid-binding immunoglobulin-like lectins (siglecs) comprise a family of receptors that are differentially expressed on leukocytes and other immune cells. The restricted expression of several siglecs to one or a few cell types makes them attractive targets for cell-directed therapies. The anti-CD33 (also kno...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: O'Reilly MK,Paulson JC

    更新日期:2009-05-01 00:00:00

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

    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

    pub_type: 杂志文章,评审


    authors: Civelli O

    更新日期:2005-01-01 00:00:00

  • Beyond vasodilatation: non-vasomotor roles of epoxyeicosatrienoic acids in the cardiovascular system.

    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


    authors: Larsen BT,Campbell WB,Gutterman DD

    更新日期:2007-01-01 00:00:00

  • Drugs of abuse: anatomy, pharmacology and function of reward pathways.

    abstract::Drugs of abuse are very powerful reinforcers, and even in conditions of limited access (where the organism is not dependent) these drugs will motivate high rates of operant responding. This presumed hedonic property and the drugs' neuropharmacological specificity provide a means of studying the neuropharmacology and n...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Koob GF

    更新日期:1992-05-01 00:00:00

  • Recent findings on the mode of action of laxatives: the role of platelet activating factor and nitric oxide.

    abstract::Platelet activating factor (PAF) is a phospholipid mediator of inflammation and stimulates anion secretion in animals and in isolated preparations of human colon. Nitric oxide (NO), synthesized from the amino acid L-arginine, is an important enteric inhibitory neurotransmitter. In addition, NO-donating compounds stimu...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Izzo AA,Gaginella TS,Mascolo N,Capasso F

    更新日期:1998-10-01 00:00:00

  • Pharmacological management of GERD: where does it stand now?

    abstract::Gastroesophageal reflux disease (GERD) is very common and advances in drug development over recent years have markedly improved GERD management. A wide range of medications are currently used in GERD treatment, including antacids, Gaviscon, sucralfate, histamine-2 receptor antagonists and prokinetics. However, proton ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Hershcovici T,Fass R

    更新日期:2011-04-01 00:00:00

  • Molecular enzymology of human liver cytosolic sulfotransferases.

    abstract::Sulfoconjugation of drugs and small xenobiotic and endogenous compounds in human tissues is primarily catalysed by cytosolic forms of sulfotransferase. In most instances, sulfate conjugation is associated with a decrease in the biological activity and an increase in the excretion of the sulfated compounds. However, su...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Falany CN

    更新日期:1991-07-01 00:00:00

  • Muscarinic agonists for senile dementia: past experience and future trends.

    abstract::Clinical experience with muscarinic agonists in the symptomatic treatment of Alzheimer's disease includes studies of the effects of pilocarpine, arecoline, bethanechol, oxotremorine and RS 86. Although the results are somewhat conflicting, there is evidence that a subgroup of patients may respond with an improvement o...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Gray JA,Enz A,Spiegel R

    更新日期:1989-12-01 00:00:00

  • New advances in NMDA receptor pharmacology.

    abstract::N-Methyl-D-aspartate (NMDA) receptors are tetrameric ion channels containing two of four possible GluN2 subunits. These receptors have been implicated for decades in neurological diseases such as stroke, traumatic brain injury, dementia and schizophrenia. The GluN2 subunits substantially contribute to functional diver...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Ogden KK,Traynelis SF

    更新日期:2011-12-01 00:00:00

  • Targeting the Type Three Secretion System in Pseudomonas aeruginosa.

    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


    authors: Anantharajah A,Mingeot-Leclercq MP,Van Bambeke F

    更新日期:2016-09-01 00:00:00

  • Pharmacological inhibitors of MAPK pathways.

    abstract::Mitogen-activated protein kinases [MAPKs, also called extracellular signal-regulated kinases (ERKs)] are constituents of numerous signal transduction pathways, and are activated by protein kinase cascades. Intense efforts are under way to develop and evaluate compounds that target components of MAPK pathways. In this ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: English JM,Cobb MH

    更新日期:2002-01-01 00:00:00

  • Phospholipase A2 enzymes: regulation and inhibition.

    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

    pub_type: 杂志文章,评审


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

    更新日期:1993-03-01 00:00:00

  • Clinical Implications of Folate Transport in the Central Nervous System.

    abstract::Folates are essential for key biosynthetic processes in mammalian cells and play a crucial role in the maintenance of central nervous system homeostasis. Mammals lack the metabolic capacity for folate biosynthesis; hence, folate requirements are largely met through dietary sources. To date, three major folate transpor...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Alam C,Kondo M,O'Connor DL,Bendayan R

    更新日期:2020-05-01 00:00:00

  • Functional versus chemical diversity: is biodiversity important for drug discovery?

    abstract::Prospecting the full biodiversity of nature to find leads for new drugs is not necessary. Because finding leads is aimed at identifying biological activity, structure is of secondary importance. Furthermore, although natural chemical diversity might be unrivalled, functional diversity is bound to be considerably less....

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Tulp M,Bohlin L

    更新日期:2002-05-01 00:00:00

  • Discoidin Domains as Emerging Therapeutic Targets.

    abstract::Discoidin (DS) domains are found in eukaryotic and prokaryotic extracellular and transmembrane multidomain proteins. These small domains play different functional roles and can interact with phospholipids, glycans, and proteins, including collagens. DS domain-containing proteins are often involved in cellular adhesion...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Villoutreix BO,Miteva MA

    更新日期:2016-08-01 00:00:00

  • Excitatory actions of adenosine on ventricular automaticity.

    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

    pub_type: 杂志文章,评审


    authors: Hernández J,Ribeiro JA

    更新日期:1996-04-01 00:00:00

  • Tumour necrosis factor alpha and interleukin 1 signalling: do MAPKK kinases connect it all?

    abstract::The potent pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1) are capable of triggering biologically similar effects through activation of the same set of transcription factors. Based on recent findings it is now becoming evident that certain members of the mitogen-activated p...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Eder J

    更新日期:1997-09-01 00:00:00

  • 007 (x2)-3-3: 14-3-3 Targeted Compounds as Double Agents.

    abstract::14-3-3 Proteins enact a range of cellular functions through protein-protein interactions (PPIs) with client proteins. Kaplan and colleagues recently demonstrated that a semisynthetic compound was able to selectively stabilize or disrupt specific interactions, depending on the binding partner. This finding presents an ...

    journal_title:Trends in pharmacological sciences

    pub_type: 评论,杂志文章


    authors: Gannon M,Yacoubian TA

    更新日期:2020-07-01 00:00:00

  • Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.

    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


    authors: Fukata Y,Amano M,Kaibuchi K

    更新日期:2001-01-01 00:00:00

  • Hormone and growth factor receptor-mediated regulation of phospholipase C activity.

    abstract::The broad importance of receptor-activated phosphoinositide hydrolysis in the physiological action of hormones, neurotransmitters and growth factors has sparked interest in the study of transmembrane signalling events responsible for activation of phospholipase C. As with receptors involved in regulation of adenylyl c...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Boyer JL,Hepler JR,Harden TK

    更新日期:1989-09-01 00:00:00

  • Molecular biology of 5-HT receptors.

    abstract::Within the past six months, isolation of cDNA or genomic clones has been reported for three 5-HT receptors, the 5-HT1C, 5-HT1A and 5-HT2 subtypes. As members of the G protein receptor superfamily, all three 5-HT receptor clones encode single-subunit proteins containing approximately 450 amino acids arrayed as seven in...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Hartig PR

    更新日期:1989-02-01 00:00:00

  • Acquired somatic mutations in the molecular pathogenesis of COPD.

    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

    pub_type: 杂志文章,评审


    authors: Anderson GP,Bozinovski S

    更新日期:2003-02-01 00:00:00

  • In-vivo brain dialysis of neurotransmitters.

    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


    authors: Di Chiara G

    更新日期:1990-03-01 00:00:00

  • Eosinophil lysis and free granules: an in vivo paradigm for cell activation and drug development.

    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

    pub_type: 杂志文章,评审


    authors: Persson CG,Erjefält JS

    更新日期:1997-04-01 00:00:00

  • Sphingosine Kinase 2 in Autoimmune/Inflammatory Disease and the Development of Sphingosine Kinase 2 Inhibitors.

    abstract::The purpose of this Opinion is to present a case for targeting sphingosine kinase 2 (SK2) in autoimmune/inflammatory disease. Data obtained using Sphk2-/- mice suggest that SK2 is an anti-inflammatory enzyme, although this might be misleading because of a compensatory increase in the expression of a second isoform, sp...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Pyne NJ,Adams DR,Pyne S

    更新日期:2017-07-01 00:00:00