共 94 条
Improved reporter gene assays used to identify ligands acting on orphan seven-transmembrane receptors
被引:53
作者:

Kotarsky, K
论文数: 0 引用数: 0
h-index: 0
机构:
Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Mol Neurobiol, S-22184 Lund, Sweden Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Mol Neurobiol, S-22184 Lund, Sweden

Nilsson, NE
论文数: 0 引用数: 0
h-index: 0
机构:
Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Mol Neurobiol, S-22184 Lund, Sweden Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Mol Neurobiol, S-22184 Lund, Sweden

Olde, B
论文数: 0 引用数: 0
h-index: 0
机构:
Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Mol Neurobiol, S-22184 Lund, Sweden Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Mol Neurobiol, S-22184 Lund, Sweden

Owman, C
论文数: 0 引用数: 0
h-index: 0
机构:
Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Mol Neurobiol, S-22184 Lund, Sweden Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Mol Neurobiol, S-22184 Lund, Sweden
机构:
[1] Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Mol Neurobiol, S-22184 Lund, Sweden
来源:
PHARMACOLOGY & TOXICOLOGY
|
2003年
/
93卷
/
06期
关键词:
D O I:
10.1111/j.1600-0773.2003.pto930601.x
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
Seven-transmembrane G-protein-coupled receptors play a central role in physiology by facilitating cell communication through recognition of a wide range of ligands. Even more important, they represent important drug targets. Unfortunately, for many of these receptors the endogenous ligands, and hence their functions, remain to be identified. These receptors are referred to as "orphan" receptors. A pre-requisite for the identification of ligands activating orphan receptors is powerful assay systems. Until now, reporter gene assays have not been in common use in this process. Here, we summarize our development of improved reporter gene assays. We optimized reporter gene assays in respect of (i) the promoter region of the construct, (ii) the reporter enzyme used, (iii) and the assay procedure. Furthermore, an unique fluorescence-based clone selection step was introduced, allowing rapid selection of the most sensitive reporter cell clones when establishing stable reporter cell lines. Mathematical formulae are provided to enable a simple and reliable comparison between different cell lines, when tested with a compound of interest. The resulting reporter cell lines responded in a very sensitive way to the stimulation of various test receptors. The reporter system was termed HighTRACE(R) (high-throughput reporter assay with clone election). Its high assay quality makes it suitable as a primary screening tool. Ligands for two recently unknown 7TM receptors were identified using the HighTRACE(R) system i.e., two cell surface free fatty acid receptors, GPR40 (FFA(1)R) and GPR43 (FFA(2)R). The identification was accomplished using a reverse pharmacology approach.
引用
收藏
页码:249 / 258
页数:10
相关论文
共 94 条
- [1] Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 231 (03) : 619 - 622An, SZ论文数: 0 引用数: 0 h-index: 0机构: UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143 UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143Dickens, MA论文数: 0 引用数: 0 h-index: 0机构: UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143 UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143Bleu, T论文数: 0 引用数: 0 h-index: 0机构: UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143 UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143Hallmark, OG论文数: 0 引用数: 0 h-index: 0机构: UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143 UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143Goetzl, EJ论文数: 0 引用数: 0 h-index: 0机构: UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143 UNIV CALIF SAN FRANCISCO,MED CTR,DEPT MICROBIOL IMMUNOL,SAN FRANCISCO,CA 94143
- [2] Rhodopsin crystal: new template yielding realistic models of G-protein-coupled receptors?[J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2003, 24 (01) : 36 - 40Archer, E论文数: 0 引用数: 0 h-index: 0机构: CHU Rangueil, Inst Louis Bugnard, INSERM, U 531, F-31403 Toulouse, FranceMaigret, B论文数: 0 引用数: 0 h-index: 0机构: CHU Rangueil, Inst Louis Bugnard, INSERM, U 531, F-31403 Toulouse, FranceEscrieut, C论文数: 0 引用数: 0 h-index: 0机构: CHU Rangueil, Inst Louis Bugnard, INSERM, U 531, F-31403 Toulouse, FrancePradayrol, L论文数: 0 引用数: 0 h-index: 0机构: CHU Rangueil, Inst Louis Bugnard, INSERM, U 531, F-31403 Toulouse, FranceFourmy, D论文数: 0 引用数: 0 h-index: 0机构: CHU Rangueil, Inst Louis Bugnard, INSERM, U 531, F-31403 Toulouse, France
- [3] Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1)[J]. FEBS LETTERS, 1999, 457 (03) : 522 - 524Bächner, D论文数: 0 引用数: 0 h-index: 0机构: Univ Hamburg, Inst Zellbiochem & Klin Neurobiol, D-20246 Hamburg, GermanyKreienkamp, HJ论文数: 0 引用数: 0 h-index: 0机构: Univ Hamburg, Inst Zellbiochem & Klin Neurobiol, D-20246 Hamburg, GermanyWeise, C论文数: 0 引用数: 0 h-index: 0机构: Univ Hamburg, Inst Zellbiochem & Klin Neurobiol, D-20246 Hamburg, GermanyBuck, F论文数: 0 引用数: 0 h-index: 0机构: Univ Hamburg, Inst Zellbiochem & Klin Neurobiol, D-20246 Hamburg, GermanyRichter, D论文数: 0 引用数: 0 h-index: 0机构: Univ Hamburg, Inst Zellbiochem & Klin Neurobiol, D-20246 Hamburg, Germany
- [4] A beta-arrestin green fluorescent protein biosensor for detecting G protein-coupled receptor activation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (44) : 27497 - 27500Barak, LS论文数: 0 引用数: 0 h-index: 0机构: DUKE UNIV,MED CTR,HOWARD HUGHES MED INST LABS,DURHAM,NC 27710Ferguson, SSG论文数: 0 引用数: 0 h-index: 0机构: DUKE UNIV,MED CTR,HOWARD HUGHES MED INST LABS,DURHAM,NC 27710Zhang, J论文数: 0 引用数: 0 h-index: 0机构: DUKE UNIV,MED CTR,HOWARD HUGHES MED INST LABS,DURHAM,NC 27710Caron, MG论文数: 0 引用数: 0 h-index: 0机构: DUKE UNIV,MED CTR,HOWARD HUGHES MED INST LABS,DURHAM,NC 27710
- [5] Neurobiology of the Caenorhabditis elegans genome[J]. SCIENCE, 1998, 282 (5396) : 2028 - 2033Bargmann, CI论文数: 0 引用数: 0 h-index: 0机构: Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
- [6] Molecular tinkering of G protein-coupled receptors: an evolutionary success[J]. EMBO JOURNAL, 1999, 18 (07) : 1723 - 1729Bockaert, J论文数: 0 引用数: 0 h-index: 0机构: CCIPE, CNRS, UPR 9023, F-34094 Montpellier 5, France CCIPE, CNRS, UPR 9023, F-34094 Montpellier 5, FrancePin, JP论文数: 0 引用数: 0 h-index: 0机构: CCIPE, CNRS, UPR 9023, F-34094 Montpellier 5, France CCIPE, CNRS, UPR 9023, F-34094 Montpellier 5, France
- [7] Characterization of the cloned guinea pig leukotriene B4 receptor:: comparison to its human orthologue[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 380 (2-3) : 203 - 213Boie, Y论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaStocco, R论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaSawyer, N论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaGreig, GM论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaKargman, S论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaSlipetz, DM论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaO'Neill, GP论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaShimizu, T论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaYokomizo, T论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaMetters, KM论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, CanadaAbramovitz, M论文数: 0 引用数: 0 h-index: 0机构: Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, Canada
- [8] Induction of NFAT-mediated transcription by G(q)-coupled receptors in lymphoid and non-lymphoid cells[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (18) : 10429 - 10432Boss, V论文数: 0 引用数: 0 h-index: 0机构: EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322 EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322Talpade, DJ论文数: 0 引用数: 0 h-index: 0机构: EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322 EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322Murphy, TJ论文数: 0 引用数: 0 h-index: 0机构: EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322 EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322
- [9] The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (13) : 11303 - 11311Briscoe, CP论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USA GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USATadayyon, M论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAAndrews, JL论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USABenson, WG论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAChambers, JK论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAEilert, MM论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAEllis, C论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAElshourbagy, NA论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAGoetz, AS论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAMinnick, DT论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAMurdock, PR论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USASauls, HR论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAShabon, U论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USASpinage, LD论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAStrum, JC论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USASzekeres, PG论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USATan, KB论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAWay, JM论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAIgnar, DM论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAWilson, S论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USAMuir, AI论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USA
- [10] The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (13) : 11312 - 11319Brown, AJ论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandGoldsworthy, SM论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandBarnes, AA论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandEilert, MM论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandTcheang, L论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandDaniels, D论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandMuir, AI论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandWigglesworth, MJ论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandKinghorn, I论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandFraser, NJ论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandPike, NB论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandStrum, JC论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandSteplewski, KM论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandMurdock, PR论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandHolder, JC论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandMarshall, FH论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandSzekeres, PG论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandWilson, S论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandIgnar, DM论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandFoord, SM论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandWise, A论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, EnglandDowell, SJ论文数: 0 引用数: 0 h-index: 0机构: GlaxoSmithKline, Med Res Ctr, Dept Syst Res 7TMR, Stevenage SG1 2NY, Herts, England