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
  • A mechanism for P-glycoprotein action in multidrug resistance: are we there yet?

    abstract::Multidrug resistance is associated with the overexpression of P-glycoprotein, a membrane glycoprotein. The mechanism by which P-glycoprotein confers to cells the capacity to resist cytotoxic attack by structurally unrelated drugs has remained difficult to decipher. However, the recent functional expression of this gro...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(94)90322-0

    authors: Ruetz S,Gros P

    更新日期:1994-07-01 00:00:00

  • Targeting SREBPs for treatment of the metabolic syndrome.

    abstract::Over the past few decades, mortality resulting from cardiovascular disease (CVD) steadily decreased in western countries; however, in recent years, the decline has become offset by the increase in obesity. Obesity is strongly associated with the metabolic syndrome and its atherogenic dyslipidemia resulting from insuli...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2015.04.010

    authors: Soyal SM,Nofziger C,Dossena S,Paulmichl M,Patsch W

    更新日期:2015-06-01 00:00:00

  • Off-target effects associated with long dsRNAs in Drosophila RNAi screens.

    abstract::Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29bp) in mammalian cells has existed for several years. Two recent articles demonstrate that short sequences within long double-stranded (ds)RNAs frequently cause undesirable OTEs in cultured Drosophila cells. These results reveal the...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.tips.2007.02.009

    authors: Moffat J,Reiling JH,Sabatini DM

    更新日期:2007-04-01 00:00:00

  • Distribution and anchoring of molecular forms of acetylcholinesterase.

    abstract::Molecular forms of acetylcholinesterase exhibit tissue-specific distribution, and each form is anchored to the cell surface via a particular post-translational modification of the catalytic subunit. Nibaldo Inestrosa and Alejandra Perelman review evidence that heparan sulphate proteoglycans are the extracellular matri...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(89)90067-9

    authors: Inestrosa NC,Perelman A

    更新日期:1989-08-01 00:00:00

  • 5-HT2 receptor subtypes: a family re-united?

    abstract::The current classification for 5-HT2 receptors accommodates three subtypes. In addition to the originally defined 5-HT2 receptor, sanctuary is now provided for the structurally related 5-HT1c receptor (now 5-HT2c) and at least one atypical 5-HT receptor subtype. The strong functional union of this family is reflected ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(00)88991-9

    authors: Baxter G,Kennett G,Blaney F,Blackburn T

    更新日期:1995-03-01 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

    doi:10.1016/0165-6147(90)90197-g

    authors: Di Chiara G

    更新日期:1990-03-01 00:00:00

  • NSAIDs: small molecules for prevention of Alzheimer's disease or precursors for future drug development?

    abstract::Non-steroidal anti-inflammatory drugs (NSAIDs) have been considered for treatment and prevention of Alzheimer's disease (AD) for more than two decades. Biochemical markers in the brains of individuals with AD suggest that inflammation might be a driving cause of the disease that can be suppressed by drug treatment. In...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2007.09.004

    authors: Weggen S,Rogers M,Eriksen J

    更新日期:2007-10-01 00:00:00

  • A three-state receptor model of agonist action.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(97)01105-x

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

    更新日期:1997-10-01 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

  • Drug-lipid interaction evaluation: why a 19th century solution?

    abstract::The affinity of a drug candidate for a biological membrane (its lipophilicity) is closely related to the pharmacologically crucial events of absorption, biodistribution, metabolization and excretion. The evolution of knowledge of biological membranes during the past two decades contrasts with the rudimentary parameter...

    journal_title:Trends in pharmacological sciences

    pub_type: 历史文章,杂志文章

    doi:10.1016/j.tips.2010.06.007

    authors: Ribeiro MM,Melo MN,Serrano ID,Santos NC,Castanho MA

    更新日期:2010-10-01 00:00:00

  • The darker side of Ca2+ signaling by neuronal Ca2+-sensor proteins: from Alzheimer's disease to cancer.

    abstract::Neuronal Ca2+-sensor (NCS) proteins constitute a subfamily of closely related EF-hand Ca2+-binding proteins that are expressed mainly in neurons or retinal photoreceptor cells. A variety of different neuronal functions have been attributed to these proteins. However, important new discoveries indicate that these prote...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2005.04.008

    authors: Braunewell KH

    更新日期:2005-07-01 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

    doi:10.1016/j.tips.2016.06.003

    authors: Villoutreix BO,Miteva MA

    更新日期:2016-08-01 00:00:00

  • Techniques: reporter mice - a new way to look at drug action.

    abstract::During the past decade remarkable progress in molecular genetics and the possibility of manipulating cells so that the expression of genes can directly 'report' on drug activity has produced major changes in drug development strategies. The recent description and pharmacological validation of reporter mice for in vivo...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2004.04.007

    authors: Maggi A,Ottobrini L,Biserni A,Lucignani G,Ciana P

    更新日期:2004-06-01 00:00:00

  • Therapeutic Targeting of Siglecs using Antibody- and Glycan-Based Approaches.

    abstract::The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of immunomodulatory receptors whose functions are regulated by their glycan ligands. Siglecs are attractive therapeutic targets because of their cell type-specific expression pattern, endocytic properties, high expression on certain lymphomas/l...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2015.06.008

    authors: Angata T,Nycholat CM,Macauley MS

    更新日期:2015-10-01 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

  • 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

    doi:10.1016/j.tips.2016.05.011

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

    更新日期:2016-09-01 00:00:00

  • The Action Radius of Oxytocin Release in the Mammalian CNS: From Single Vesicles to Behavior.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2017.08.005

    authors: Chini B,Verhage M,Grinevich V

    更新日期:2017-11-01 00:00:00

  • Insight into the Structural Features of TSPO: Implications for Drug Development.

    abstract::The translocator protein (TSPO), an 18-kDa transmembrane protein primarily found in the outer mitochondrial membrane, is evolutionarily conserved and widely distributed across species. In mammals, TSPO has been described as a key member of a multiprotein complex involved in many putative functions and, over the years,...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2019.11.005

    authors: Lacapere JJ,Duma L,Finet S,Kassiou M,Papadopoulos V

    更新日期:2020-02-01 00:00:00

  • Intracellular 5-HT 2C-receptor dephosphorylation: a new target for treating drug addiction.

    abstract::The 5-hydroxytryptamine (5-HT)(2C) receptor has received considerable attention as a target for treating drug addiction. 5-HT(2C)-receptor agonism, however, also induces side-effects. In this article, we review recent findings regarding the involvement of 5-HT(2C) receptors in behaviours related to drug addiction in a...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2006.07.003

    authors: Müller CP,Carey RJ

    更新日期:2006-09-01 00:00:00

  • Regulation of vascular reactivity by established and emerging GPCRs.

    abstract::The vascular system is rich in G-protein-coupled receptors (GPCRs), particularly Class 1 GPCRs, which are activated by an eclectic range of chemical entities including peptides. These chemical messengers can function in blood vessels as directly acting vasoconstrictors, directly acting vasodilators or indirectly actin...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.tips.2005.07.007

    authors: Maguire JJ,Davenport AP

    更新日期:2005-09-01 00:00:00

  • Developing analgesics by enhancing spinal inhibition after injury: GABAA receptor subtypes as novel targets.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2009.06.004

    authors: Munro G,Ahring PK,Mirza NR

    更新日期:2009-09-01 00:00:00

  • Physiological relevance of constitutive activity of 5-HT2A and 5-HT2C receptors.

    abstract::It is generally accepted that seven-transmembrane receptors have the capacity to regulate cellular signaling systems in the absence of occupancy by a ligand (i.e. the receptors display constitutive activity). Drugs can increase (agonists), decrease (inverse agonists) or not change (antagonists) receptor activity towar...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2005.10.008

    authors: Berg KA,Harvey JA,Spampinato U,Clarke WP

    更新日期:2005-12-01 00:00:00

  • Toxicology of simple and complex mixtures.

    abstract::Humans are exposed to mixtures of chemicals, rather than to individual chemicals. From a public health point of view, it is most relevant to answer the question of whether or not the components in a mixture interact in a way that results in an increase in their overall effect compared with the sum of the effects of th...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(00)01720-x

    authors: Groten JP,Feron VJ,Sühnel J

    更新日期:2001-06-01 00:00:00

  • Pharmacological tools for the development of traditional Chinese medicine.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2013.09.004

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

    更新日期:2013-11-01 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

  • Pilot the pulse: controlling the multiplicity of receptor dynamics.

    abstract::G protein-coupled receptors (GPCRs) are involved in almost every (patho)physiological process, which explains their importance as drug targets. GPCRs have long been regarded as on/off-switches, which is reflected by direct activation or blockade of these receptors through the majority of marketed GPCR drugs. In recent...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.tips.2014.10.002

    authors: Bock A,Kostenis E,Tränkle C,Lohse MJ,Mohr K

    更新日期:2014-12-01 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

  • Protein kinase Calpha: disease regulator and therapeutic target.

    abstract::Protein kinase Calpha (PKCalpha) is a member of the AGC (which includes PKD, PKG and PKC) family of serine/threonine protein kinases that is widely expressed in mammalian tissues. It is closely related in structure, function and regulation to other members of the protein kinase C family, but has specific functions wit...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2009.10.006

    authors: Konopatskaya O,Poole AW

    更新日期:2010-01-01 00:00:00

  • Gene targeting--homing in on alpha 2-adrenoceptor-subtype function.

    abstract::The alpha-adrenoceptor was subdivided into three subtypes: alpha 2A-, alpha 2B- and alpha 2C-adrenoceptors almost ten years ago. Since then, the search has been on to discover and develop subtype-selective agonists and antagonists, but as yet no major breakthrough has been made. In the past year, several strains of ge...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(97)01063-8

    authors: MacDonald E,Kobilka BK,Scheinin M

    更新日期:1997-06-01 00:00:00

  • Regulation of free calmodulin levels by neuromodulin: neuron growth and regeneration.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(90)90195-e

    authors: Liu YC,Storm DR

    更新日期:1990-03-01 00:00:00