RGS9-2: probing an intracellular modulator of behavior as a drug target.

Abstract:

:Regulators of G-protein signaling (RGS proteins) comprise a large family of signal transduction molecules that modulate G-protein-coupled-receptor (GPCR) function. Among the RGS proteins expressed in the brain, RGS9-2 is very abundant in the striatum, a brain region involved in movement, motivation, mood and addiction. This protein negatively modulates signal transduction thus playing a key part in striatal function and resultant behavioral responses. In particular, there is evidence of important interactions with mu-opioid- and dopamine D(2)-receptor signaling pathways. Several studies indicate that manipulations of RGS9-2 levels in the striatum might greatly affect pharmacological responses. These findings indicate that treatment strategies targeting RGS9-2 levels or activity might be used to enhance responses to drugs acting at GPCRs and/or prevent undesired drug actions.

journal_name

Trends Pharmacol Sci

authors

Traynor JR,Terzi D,Caldarone BJ,Zachariou V

doi

10.1016/j.tips.2008.11.006

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

105-11

issue

3

eissn

0165-6147

issn

1873-3735

pii

S0165-6147(09)00014-5

journal_volume

30

pub_type

杂志文章
  • Reactivation of p53: from peptides to small molecules.

    abstract::Approximately 27 million people are living with a tumour in which the tumour suppressing activity of p53 has been inactivated. In half of these tumours, p53 itself is not mutated but the pathway is partially abrogated. Mechanisms include the overexpression of negative regulators of p53, such as MDM2 and MDM4, and dele...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2010.11.004

    authors: Brown CJ,Cheok CF,Verma CS,Lane DP

    更新日期:2011-01-01 00:00:00

  • Assay strategies for identification of therapeutic leads that target protein trafficking.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2015.05.004

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

    更新日期:2015-08-01 00:00:00

  • Peptides for cell-selective drug delivery.

    abstract::The ability to target specific cell types to achieve optimal distribution of therapeutic entities into diseased tissues, while limiting possible adverse off-target effects, has long been a goal of many research groups and pharmaceutical organizations. This review focuses on peptidic tissue-specific biomarkers that all...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2012.02.002

    authors: Svensen N,Walton JG,Bradley M

    更新日期:2012-04-01 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

    doi:10.1016/0165-6147(89)90008-4

    authors: Boyer JL,Hepler JR,Harden TK

    更新日期:1989-09-01 00:00:00

  • Control of transmitter release from the motor nerve by presynaptic nicotinic and muscarinic autoreceptors.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(89)90208-3

    authors: Wessler I

    更新日期:1989-03-01 00:00:00

  • How and why do GPCRs dimerize?

    abstract::Dimerization is fairly common in the G-protein-coupled receptor (GPCR) superfamily. First attempts to rationalize this phenomenon gave rise to an idea that two receptors in a dimer could be necessary to bind a single molecule of G protein or arrestin. Although GPCRs, G proteins and arrestins were crystallized only in ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.tips.2008.02.004

    authors: Gurevich VV,Gurevich EV

    更新日期:2008-05-01 00:00:00

  • Historical review: a brief history and personal retrospective of seven-transmembrane receptors.

    abstract::Pharmacologists have studied receptors for more than a century but a molecular understanding of their properties has emerged only during the past 30-35 years. In this article, I provide a personal retrospective of how developments and discoveries primarily during the 1970s and 1980s led to current concepts about the l...

    journal_title:Trends in pharmacological sciences

    pub_type: 历史文章,杂志文章

    doi:10.1016/j.tips.2004.06.006

    authors: Lefkowitz RJ

    更新日期:2004-08-01 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

    doi:10.1016/j.tips.2006.11.002

    authors: Larsen BT,Campbell WB,Gutterman DD

    更新日期:2007-01-01 00:00:00

  • Training the Circadian Clock, Clocking the Drugs, and Drugging the Clock to Prevent, Manage, and Treat Chronic Diseases.

    abstract::Daily rhythms in behavior, physiology, and metabolism are an integral part of homeostasis. These rhythms emerge from interactions between endogenous circadian clocks and ambient light-dark cycles, sleep-activity cycles, and eating-fasting cycles. Nearly the entire primate genome shows daily rhythms in expression in ti...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2018.07.003

    authors: Sulli G,Manoogian ENC,Taub PR,Panda S

    更新日期:2018-09-01 00:00:00

  • Analysis of competitive agonist-antagonist interactions by nonlinear regression.

    abstract::The rigorous estimation of a dissociation constant (Kb) for antagonists in functional assays has been sought by pharmacologists using a variety of techniques ever since the regression method of Arunlakshana and Schild in 1959. Here, Michael Lew and James Angus describe a simplified global regression method with improv...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(00)89066-5

    authors: Lew MJ,Angus JA

    更新日期:1995-10-01 00:00:00

  • Endocannabinoid signaling at the periphery: 50 years after THC.

    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

    authors: Maccarrone M,Bab I,Bíró T,Cabral GA,Dey SK,Di Marzo V,Konje JC,Kunos G,Mechoulam R,Pacher P,Sharkey KA,Zimmer A

    更新日期:2015-05-01 00:00:00

  • The troubled story of tachykinins and neurokinins.

    abstract::A family of peptides that shares a common C-terminal sequence (Phe-X-Gly-Leu-MetNH2) exists in mammalian and non-mammalian species. In mammals, three of these peptides (substance P, neurokinin A and neurokinin B) satisfy the criteria to be considered as neurotransmitters either in the central, peripheral or enteric ne...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/s0165-6147(00)01463-2

    authors: Maggi CA

    更新日期:2000-05-01 00:00:00

  • The pharmacology of apoptosis.

    abstract::Apoptosis is an area of intense scientific interest, which encompasses the study of and triggers mechanisms involved in mediating the cell biology of programmed cell death. A number of low molecular weight compounds have been used to inhibit or enhance this fundamental cellular process and so apoptosis has now become ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(98)01277-2

    authors: Kinloch RA,Treherne JM,Furness LM,Hajimohamadreza I

    更新日期:1999-01-01 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

    doi:10.1016/j.tips.2011.08.003

    authors: Ogden KK,Traynelis SF

    更新日期:2011-12-01 00:00:00

  • The pathophysiology and pharmacology of hepcidin.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2014.01.004

    authors: Ruchala P,Nemeth E

    更新日期:2014-03-01 00:00:00

  • Non-genomic and genomic effects of steroids on neural activity.

    abstract::Steroid hormones are recognized as producing their major long-term effects on cell structure and function via intracellular receptors acting on the expression of genes. There is now increasing evidence that steroids also affect the surface of cells and alter ion permeability, as well as release of neurohormones and ne...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(91)90531-v

    authors: McEwen BS

    更新日期:1991-04-01 00:00:00

  • An emerging role for PtdIns(4,5)P2-mediated signalling in human disease.

    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

    authors: Halstead JR,Jalink K,Divecha N

    更新日期:2005-12-01 00:00:00

  • Characterization of the action of antipsychotic subtypes on valproate-induced chromatin remodeling.

    abstract::Recent advances in schizophrenia (SZ) research indicate that the telencephalic gamma-aminobutyric acid (GABA)ergic neurotransmission deficit associated with this psychiatric disorder probably is mediated by the hypermethylation of the glutamic acid decarboxylase 67 (GAD(67)), reelin and other GABAergic promoters. A ph...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.tips.2008.10.010

    authors: Guidotti A,Dong E,Kundakovic M,Satta R,Grayson DR,Costa E

    更新日期:2009-02-01 00:00:00

  • Muscarinic activation of potassium channels in cardiac myocytes: kinetic aspects of G protein function in vivo.

    abstract::Muscarinic agonists open potassium-selective K(ACh) channels in cardiac myocytes of pacemaker or atrial origin. Receptor activation is coupled to channel opening by a membrane bound guanine nucleotide-binding protein (GK) through a process that does not require cytoplasmic intermediates. We have used the muscarinic po...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:

    authors: Szabo G,Otero AS

    更新日期:1989-12-01 00:00:00

  • Precision Medicine through Antisense Oligonucleotide-Mediated Exon Skipping.

    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

    authors: Li D,Mastaglia FL,Fletcher S,Wilton SD

    更新日期:2018-11-01 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

    doi:10.1016/j.tips.2011.02.007

    authors: Hershcovici T,Fass R

    更新日期:2011-04-01 00:00:00

  • Higher-order organization and regulation of adenylyl cyclases.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2006.06.002

    authors: Cooper DM,Crossthwaite AJ

    更新日期:2006-08-01 00:00:00

  • Regulation of transcription factor activity by interconnected post-translational modifications.

    abstract::Transcription factors comprise just over 7% of the human proteome and serve as gatekeepers of cellular function, integrating external signal information into gene expression programs that reconfigure cellular physiology at the most basic levels. Surface-initiated cell signaling pathways converge on transcription facto...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2013.11.005

    authors: Filtz TM,Vogel WK,Leid M

    更新日期:2014-02-01 00:00:00

  • Resolution of airway disease: removal of inflammatory cells through apoptosis, egression or both?

    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

    pub_type: 杂志文章

    doi:10.1016/j.tips.2006.07.006

    authors: Uller L,Persson CG,Erjefält JS

    更新日期:2006-09-01 00:00:00

  • Targeting the melanocortin receptor system for anti-stroke therapy.

    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

    authors: Holloway PM,Smith HK,Renshaw D,Flower RJ,Getting SJ,Gavins FN

    更新日期:2011-02-01 00:00:00

  • Cooperativity Has Empirical and Ultimate Levels of Explanation.

    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 Figur...

    journal_title:Trends in pharmacological sciences

    pub_type: 评论,信件

    doi:10.1016/j.tips.2016.06.001

    authors: Ehlert FJ

    更新日期:2016-08-01 00:00:00

  • Frizzleds as GPCRs - More Conventional Than We Thought!

    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

    authors: Schulte G,Wright SC

    更新日期:2018-09-01 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

    doi:10.1016/0165-6147(96)81589-6

    authors: Hernández J,Ribeiro JA

    更新日期:1996-04-01 00:00:00

  • Genomic and proteomic strategies to identify novel targets potentially involved in learning and memory.

    abstract::The hippocampus is a crucial player across several learning and memory domains, and is highly vulnerable to alterations during aging. Several products of neurotransmitter genes and neuromodulator genes (which play important parts in mediating and maintaining cognitive ability as a function of age) are expressed in hip...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2010.10.002

    authors: Benoit CE,Rowe WB,Menard C,Sarret P,Quirion R

    更新日期:2011-01-01 00:00:00

  • Targeting tumor-associated carbonic anhydrase IX in cancer therapy.

    abstract::Carbonic anhydrase isoform IX (CA IX) is highly overexpressed in many types of cancer. Its expression, which is regulated by the HIF-1 transcription factor, is strongly induced by hypoxia and correlates with a poor response to classical chemo- and radiotherapies. CA IX contributes to acidification of the tumor environ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.tips.2006.09.002

    authors: Thiry A,Dogné JM,Masereel B,Supuran CT

    更新日期:2006-11-01 00:00:00