Constitutive endocytic cycle of the CB1 cannabinoid receptor.
AuthorsLeterrier C, Bonnard D, Carrel D, Rossier J, Lenkei Z
JournalJ Biol Chem
PubMed ID15210689
'The CB1 cannabinoid receptor (CB1R) displays a significant level of ligand-independent (i.e. constitutive) activity, either when heterologously expressed in nonneuronal cells or in neurons where CB1Rs are endogenous. The present study investigates the consequences of constitutive activity on the intracellular trafficking of CB1R. When transfected in HEK-293 cells, CB1R is ... More
A G protein-coupled receptor responsive to bile acids.
AuthorsKawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M, Fukusumi S, Habata Y, Itoh T, Shintani Y, Hinuma S, Fujisawa Y, Fujino M
JournalJ Biol Chem
PubMed ID12524422
'So far some nuclear receptors for bile acids have been identified. However, no cell surface receptor for bile acids has yet been reported. We found that a novel G protein-coupled receptor, TGR5, is responsive to bile acids as a cell-surface receptor. Bile acids specifically induced receptor internalization, the activation of ... More
The regulation of feeding and metabolic rate and the prevention of murine cancer cachexia with a small-molecule melanocortin-4 receptor antagonist.
AuthorsMarkison S, Foster AC, Chen C, Brookhart GB, Hesse A, Hoare SR, Fleck BA, Brown BT, Marks DL
JournalEndocrinology
PubMed ID15774557
'Cachexia is metabolic disorder characterized by anorexia, an increased metabolic rate, and loss of lean body mass. It is a relatively common disorder, and is a pathological feature of diseases such as cancer, HIV infection, and renal failure. Recent studies have demonstrated that cachexia brought about by a variety of ... More
Immunomodulatory mediators from pollen enhance the migratory capacity of dendritic cells and license them for Th2 attraction.
AuthorsMariani V, Gilles S, Jakob T, Thiel M, Mueller MJ, Ring J, Behrendt H, Traidl-Hoffmann C
JournalJ Immunol
PubMed ID17548598
'The immune response of atopic individuals against allergens is characterized by increased levels of Th2 cytokines and chemokines. However, the way in which the cytokine/chemokine profile is matched to the type of invading allergen, and why these profiles sometimes derail and lead to disease, is not well understood. We recently ... More
Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach.
AuthorsGupte J, Cutler G, Chen JL, Tian H,
JournalProc Natl Acad Sci U S A
PubMed ID14757815
'The identification of endogenous or surrogate ligands for orphan G protein-coupled receptors (GPCRs) represents one of the most important tasks in GPCR biology and pharmacology. The challenge lies in choosing an appropriate assay in the absence of ways to activate the receptor of interest. We investigated the signaling pathway for ... More
Short bioactive Spiegelmers to migraine-associated calcitonin gene-related peptide rapidly identified by a novel approach: tailored-SELEX.
AuthorsVater A, Jarosch F, Buchner K, Klussmann S,
JournalNucleic Acids Res
PubMed ID14576330
'We developed an integrated method to identify aptamers with only 10 fixed nucleotides through ligation and removal of primer binding sites within the systematic evolution of ligands by exponential enrichment (SELEX) process. This Tailored-SELEX approach was validated by identifying a Spiegelmer (''mirror-image aptamer'') that inhibits the action of the migraine-associated ... More
Identification and characterization of a cell-surface receptor, P2Y15, for AMP and adenosine.
AuthorsInbe H, Watanabe S, Miyawaki M, Tanabe E, Encinas JA,
JournalJ Biol Chem
PubMed ID15001573
'AMP and adenosine are found in all cell types and can be released by cells or created extracellularly from the breakdown of ATP and ADP. We have identified an orphan G protein-coupled receptor with homology to the P2Y family of nucleotide receptors that can respond to both AMP and adenosine. ... More
Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors.
AuthorsHe W, Miao FJ, Lin DC, Schwandner RT, Wang Z, Gao J, Chen JL, Tian H, Ling L,
JournalNature
PubMed ID15141213
'The citric acid cycle is central to the regulation of energy homeostasis and cell metabolism. Mutations in enzymes that catalyse steps in the citric acid cycle result in human diseases with various clinical presentations. The intermediates of the citric acid cycle are present at micromolar concentration in blood and are ... More
P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries.
AuthorsAndre P, Delaney SM, LaRocca T, Vincent D, DeGuzman F, Jurek M, Koller B, Phillips DR, Conley PB,
JournalJ Clin Invest
PubMed ID12897207
'The critical role for ADP in arterial thrombogenesis was established by the clinical success of P2Y12 antagonists, currently used at doses that block 40-50% of the P2Y12 on platelets. This study was designed to determine the role of P2Y12 in platelet thrombosis and how its complete absence affects the thrombotic ... More
Interferon-gamma down-regulates adenosine 2b receptor-mediated signaling and short circuit current in the intestinal epithelia by inhibiting the expression of adenylate cyclase.
'Adenosine is an endogenous signaling molecule that is highly up-regulated in inflammatory states. Adenosine acts through the A2b receptor, a G protein-coupled receptor that couples positively to Galpha(s) and activates adenylate cyclase. This leads to cAMP-mediated electrogenic chloride secretion in intestinal epithelia. To better understand the regulation of the A2b ... More
Benzodioxoles: novel cannabinoid-1 receptor inverse agonists for the treatment of obesity.
AuthorsAlig L, Alsenz J, Andjelkovic M, Bendels S, Bénardeau A, Bleicher K, Bourson A, David-Pierson P, Guba W, Hildbrand S, Kube D, Lübbers T, Mayweg AV, Narquizian R, Neidhart W, Nettekoven M, Plancher JM, Rocha C, Rogers-Evans M, Röver S, Schneider G, Taylor S, Waldmeier P
JournalJ Med Chem
PubMed ID18335976
'The application of the evolutionary fragment-based de novo design tool TOPology Assigning System (TOPAS), starting from a known CB1R (CB-1 receptor) ligand, followed by further refinement principles, including pharmacophore compliance, chemical tractability, and drug likeness, allowed the identification of benzodioxoles as a novel CB1R inverse agonist series. Extensive multidimensional optimization ... More
ATM substrate Chk2-interacting Zn2+ finger (ASCIZ) Is a bi-functional transcriptional activator and feedback sensor in the regulation of dynein light chain (DYNLL1) expression.
AuthorsJurado S, Conlan LA, Baker EK, Ng JL, Tenis N, Hoch NC, Gleeson K, Smeets M, Izon D, Heierhorst J
JournalJ Biol Chem
PubMed ID22167198
'The highly conserved DYNLL1 (LC8) protein was originally discovered as a light chain of the dynein motor complex, but is increasingly emerging as a sequence-specific regulator of protein dimerization with hundreds of targets and wide-ranging cellular functions. Despite its important roles, DYNLL1''s own regulation remains poorly understood. Here we identify ... More
5-Oxo-eicosatetraenoic acid-induced chemotaxis: identification of a responsible receptor hGPCR48 and negative regulation by G protein G(12/13).
'While screening genes encoding G protein-coupled receptors (GPCRs) in the human genome, we and other groups have identified a GPCR named hGPCR48 as a high affinity receptor for 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is arachidonic acid metabolite and an endogenous chemoattractant for granulocytes. Using Chinese hamster ovary (CHO) cells stably expressing ... More
Structural determinants for membrane trafficking and G protein selectivity of a mouse olfactory receptor.
AuthorsKatada S, Tanaka M, Touhara K
JournalJ Neurochem
PubMed ID15341529
'The G protein-coupled olfactory receptor (OR) superfamily plays a critical role in recognizing a broad range of odorants. Each OR appears to recognize odorants based on similarities in molecular structures such that mOR-EG, a mouse OR, binds eugenol, vanillin, and some other structurally related odorants. Only a few ORs, however, ... More
Corticotropin-releasing hormone receptor (CRHR)1 and CRHR2 are both trafficking and signaling receptors for urocortin.
AuthorsTu H, Kastin AJ, Pan W,
JournalMol Endocrinol
PubMed ID17170072
'Transport of urocortin, a potent satiety peptide, occurs at the blood-brain barrier of the mouse. Endocytosis of urocortin by the cerebral microvessel endothelial cells composing the blood-brain barrier is a rate-limiting step of this transport, but the cellular mechanisms involved have not been fully elucidated. The presence of both CRH ... More
Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770.
AuthorsVan Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, Turnbull A, Singh A, Joubran J, Hazlewood A, Zhou J, McCartney J, Arumugam V, Decker C, Yang J, Young C, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu P
JournalProc Natl Acad Sci U S A
PubMed ID19846789
'Cystic fibrosis (CF) is a fatal genetic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a protein kinase A (PKA)-activated epithelial anion channel involved in salt and fluid transport in multiple organs, including the lung. Most CF mutations either reduce the number of CFTR ... More
Platelet-derived adenosine 5'-triphosphate suppresses activation of human hepatic stellate cell: In vitro study.
AuthorsIkeda N, Murata S, Maruyama T, Tamura T, Nozaki R, Kawasaki T, Fukunaga K, Oda T, Sasaki R, Homma M, Ohkohchi N
JournalHepatol Res
PubMed ID21988364
'Aim: Activated hepatic stellate cells (HSC) play a critical role in liver fibrosis. Suppressing abnormal function of HSC or reversion from activated to quiescent form is a hopeful treatment for liver cirrhosis. The interaction between platelets and HSC remains unknown although platelets go through hepatic sinusoids surrounded by HSC. ... More
Adenosine A2B receptors are highly expressed on murine type II alveolar epithelial cells.
AuthorsCagnina RE, Ramos SI, Marshall MA, Wang G, Frazier CR, Linden J
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID19574419
'The adenosine A(2B) receptor (A(2B)R) has a wide tissue distribution that includes fibroblasts and endothelial and epithelial cells. The recent generation of an A(2B)R(-/-) mouse constructed with a beta-galactosidase (beta-gal) reporter gene under control of the endogenous promoter has provided a valuable tool to quantify A(2B)R promoter activity (29). To ... More
Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity.
AuthorsMuda M, He C, Martini PG, Ferraro T, Layfield S, Taylor D, Chevrier C, Schweickhardt R, Kelton C, Ryan PL, Bathgate RA
JournalMol Hum Reprod
PubMed ID16051677
'LGR7 and LGR8 are G protein-coupled receptors that belong to the leucine-rich repeat-containing G-protein coupled receptor (LGR) family, including the thyroid-stimulating hormone (TSH), LH and FSH receptors. LGR7 and LGR8 stimulate cAMP production upon binding of the cognate ligands, relaxin and insulin-like peptide 3 (INSL3), respectively. We cloned several novel ... More
Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease.
AuthorsIijima-Ando K, Hearn SA, Shenton C, Gatt A, Zhao L, Iijima K
JournalPLoS One
PubMed ID20016833
'The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer''s disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or ... More
Allosteric ligands for the corticotropin releasing factor type 1 receptor modulate conformational states involved in receptor activation.
AuthorsHoare SR, Fleck BA, Gross RS, Crowe PD, Williams JP, Grigoriadis DE,
JournalMol Pharmacol
PubMed ID18239030
'Allosteric modulators of G-protein-coupled receptors can regulate conformational states involved in receptor activation ( Mol Pharmacol 58: 1412-1423, 2000 ). This hypothesis was investigated for the corticotropin-releasing factor type 1 (CRF(1)) receptor using a novel series of ligands with varying allosteric effect on CRF binding (inhibition to enhancement). For the ... More
Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs).
AuthorsMortensen RD, Serra M, Steitz JA, Vasudevan S
JournalProc Natl Acad Sci U S A
PubMed ID21536868
'MicroRNA-protein complexes (microRNPs) can activate translation of target reporters and specific mRNAs in quiescent (i.e., G0) mammalian cell lines. Induced quiescent cells, like folliculated immature oocytes, have high levels of cAMP that activate protein kinase AII (PKAII) to maintain G0 and immature states. We report microRNA-mediated up-regulated expression of reporters ... More
RTP family members induce functional expression of mammalian odorant receptors.
AuthorsSaito H, Kubota M, Roberts RW, Chi Q, Matsunami H
JournalCell
PubMed ID15550249
'Transport of G protein-coupled receptors (GPCRs) to the cell surface membrane is critical in order for the receptors to recognize their ligands. However, mammalian GPCR odorant receptors (ORs), when heterologously expressed in cells, are poorly expressed on the cell surface. Here we show that the transmembrane proteins RTP1 and RTP2 ... More
The A2B adenosine receptor protects against inflammation and excessive vascular adhesion.
AuthorsYang D, Zhang Y, Nguyen HG, Koupenova M, Chauhan AK, Makitalo M, Jones MR, St Hilaire C, Seldin DC, Toselli P, Lamperti E, Schreiber BM, Gavras H, Wagner DD, Ravid K
JournalJ Clin Invest
PubMed ID16823489
'Adenosine has been described as playing a role in the control of inflammation, but it has not been certain which of its receptors mediate this effect. Here, we generated an A2B adenosine receptor-knockout/reporter gene-knock-in (A2BAR-knockout/reporter gene-knock-in) mouse model and showed receptor gene expression in the vasculature and macrophages, the ablation ... More
Discovery of N-(1-ethylpropyl)-[3-methoxy-5-(2-methoxy-4-trifluoromethoxyphenyl)-6-methyl-pyrazin-2-yl]amine 59 (NGD 98-2): an orally active corticotropin releasing factor-1 (CRF-1) receptor antagonist.
AuthorsHodgetts KJ, Ge P, Yoon T, De Lombaert S, Brodbeck R, Gulianello M, Kieltyka A, Horvath RF, Kehne JH, Krause JE, Maynard GD, Hoffman D, Lee Y, Fung L, Doller D
JournalJ Med Chem
PubMed ID21618986
'The design, synthesis, and structure-activity relationships of a novel series of pyrazines, acting as corticotropin releasing factor-1 (CRF-1) receptor antagonists, are described. Synthetic methodologies were developed to prepare a number of substituted pyrazine cores utilizing regioselective halogenation and chemoselective derivatization. Noteworthy, an efficient 5-step synthesis was developed for the lead ... More
Brain cannabinoid CB2 receptor in schizophrenia.
AuthorsIshiguro H, Horiuchi Y, Ishikawa M, Koga M, Imai K, Suzuki Y, Morikawa M, Inada T, Watanabe Y, Takahashi M, Someya T, Ujike H, Iwata N, Ozaki N, Onaivi ES, Kunugi H, Sasaki T, Itokawa M, Arai M, Niizato K, Iritani S, Naka I, Ohashi J, Kakita A, Takahashi H, Nawa H, Arinami T
JournalBiol Psychiatry
PubMed ID19931854
Neural endocannabinoid function appears to be involved in schizophrenia. Two endocannabinoid receptors, CB1 and CB2, are found in the brain and elsewhere in the body. We investigated roles of CB2 in schizophrenia. ... More
Blockade of adenosine A2B receptors ameliorates murine colitis.
AuthorsKolachala V, Ruble B, Vijay-Kumar M, Wang L, Mwangi S, Figler H, Figler R, Srinivasan S, Gewirtz A, Linden J, Merlin D, Sitaraman S
JournalBr J Pharmacol
PubMed ID18536750
The adenosine 2B (A2B) receptor is the predominant adenosine receptor expressed in the colon. Acting through the A2B receptor, adenosine mediates chloride secretion, as well as fibronectin and interleukin (IL)-6 synthesis and secretion in intestinal epithelial cells. A2B receptor mRNA and protein expression are increased during human and murine colitis. ... More
Synthesis and pharmacological characterization of novel druglike corticotropin-releasing factor 1 antagonists.
AuthorsDi Fabio R, St-Denis Y, Sabbatini FM, Andreotti D, Arban R, Bernasconi G, Braggio S, Blaney FE, Capelli AM, Castiglioni E, Di Modugno E, Donati D, Fazzolari E, Ratti E, Feriani A, Contini S, Gentile G, Ghirlanda D, Provera S, Marchioro C, Roberts KL, Mingardi A, Mattioli M, Nalin A, Pavone F, Spada S, Trist DG, Worby A
JournalJ Med Chem
PubMed ID18989952
To identify new CRF(1) receptor antagonists, an attempt to modify the bis-heterocycle moiety present in the top region of the dihydropyrrole[2,3]pyridine template was made following new pharmacophoric hypothesis on the CRF(1) receptor antagonists binding pocket. In particular, the 2-thiazole ring, present in the previous series of compounds, was replaced by ... More
Design and synthesis of tricyclic corticotropin-releasing factor-1 antagonists.
AuthorsGross RS, Guo Z, Dyck B, Coon T, Huang CQ, Lowe RF, Marinkovic D, Moorjani M, Nelson J, Zamani-Kord S, Grigoriadis DE, Hoare SR, Crowe PD, Bu JH, Haddach M, McCarthy J, Saunders J, Sullivan R, Chen T, Williams JP
JournalJ Med Chem
PubMed ID16134945
Antagonists of the corticotropin-releasing factor (CRF) neuropeptide should prove to be effective in treating stress and anxiety-related disorders. In an effort to identify antagonists with improved physicochemical properties, new tricyclic CRF(1) antagonists were designed, synthesized, and tested for biological activity. As a result of studies aimed at establishing a relationship ... More
Design, synthesis, and biological studies of efficient multivalent melanotropin ligands: tools toward melanoma diagnosis and treatment.
To achieve early detection and specific cancer treatment, we propose the use of multivalent interactions in which a series of binding events leads to increased affinity and consequently to selectivity. Using melanotropin (MSH) ligands, our aim is to target melanoma cells which overexpress melanocortin receptors. In this study, we report ... More
Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells.
AuthorsNii-Kono T, Iwasaki Y, Uchida M, Fujieda A, Hosokawa A, Motojima M, Yamato H, Kurokawa K, Fukagawa M,
JournalKidney Int
PubMed ID17264878
Skeletal resistance to parathyroid hormone (PTH) is well known to the phenomenon in chronic renal failure patient, but the detailed mechanism has not been elucidated. In the process of analyzing an animal model of renal failure with low bone turnover, we demonstrated decreased expression of PTH receptor (PTHR) accompanying renal ... More
A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells.
AuthorsLappas CM, Rieger JM, Linden J,
JournalJ Immunol
PubMed ID15634932
Incubation of purified C57BL/6 murine CD4(+) T lymphocytes with anti-CD3 mAb serves as a model of TCR-mediated activation and results in increased IFN-gamma production and cell surface expression of CD25 and CD69. We demonstrate here that signaling through the TCR causes a rapid (4-h) 5-fold increase in A(2A) adenosine receptor ... More
A novel high throughput chemiluminescent assay for the measurement of cellular cyclic adenosine monophosphate levels.
AuthorsChiulli AC, Trompeter K, Palmer M,
JournalJ Biomol Screen
PubMed ID10992044
The second messenger 3', 5'-cyclic AMP (cAMP) is a highly regulated molecule that is governed by G protein-coupled receptor activation and other cellular processes. Measurement of cAMP levels in cells is widely used as an indicator of receptor function in drug discovery applications. We have developed a nonradioactive ELISA for ... More
Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies.
AuthorsSato H, Macchiarulo A, Thomas C, Gioiello A, Une M, Hofmann AF, Saladin R, Schoonjans K, Pellicciari R, Auwerx J,
JournalJ Med Chem
PubMed ID18307294
TGR5, a metabotropic receptor that is G-protein-coupled to the induction of adenylate cyclase, has been recognized as the molecular link connecting bile acids to the control of energy and glucose homeostasis. With the aim of disclosing novel selective modulators of this receptor and at the same time clarifying the molecular ... More
Synthesis and evaluation of lysophosphatidylserine analogues as inducers of mast cell degranulation. Potent activities of lysophosphatidylthreonine and its 2-deoxy derivative.
AuthorsIwashita M, Makide K, Nonomura T, Misumi Y, Otani Y, Ishida M, Taguchi R, Tsujimoto M, Aoki J, Arai H, Ohwada T
JournalJ Med Chem
PubMed ID19743861
In response to various exogenous stimuli, mast cells (MCs) release a wide variety of inflammatory mediators stored in their cytoplasmic granules and this release initiates subsequent allergic reactions. Lysophosphatidylserine (lysoPS) has been known as an exogenous inducer to potentiate histamine release from MCs, though even at submicromolar concentrations. In this ... More
Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84.
AuthorsWang J, Wu X, Simonavicius N, Tian H, Ling L
JournalJ Biol Chem
PubMed ID16966319
Free fatty acids (FFAs) play important physiological roles in many tissues as an energy source and as signaling molecules in various cellular processes. Elevated levels of circulating FFAs are associated with obesity, dyslipidemia, and diabetes. Here we show that GPR84, a previously orphan G protein-coupled receptor, functions as a receptor ... More
RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway.
AuthorsJames MA, Lu Y, Liu Y, Vikis HG, You M
JournalCancer Res
PubMed ID19244110
We have identified RGS17 as a commonly induced gene in lung and prostate tumors. Through microarray and gene expression analysis, we show that expression of RGS17 is up-regulated in 80% of lung tumors, and also up-regulated in prostate tumors. Through knockdown and overexpression of RGS17 in tumor cells, we show ... More
Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor.
AuthorsSchwarz DA, Barry G, Eliasof SD, Petroski RE, Conlon PJ, Maki RA
JournalJ Biol Chem
PubMed ID10906333
We have identified a splice variant encoding only the extracellular ligand-binding domain of the gamma-aminobutyric acid B (GABA(B)) receptor subunit GABA(B(1a)). This isoform, which we have named GABA(B(1e)), is detected in both rats and humans. While GABA(B(1e)) is a minor component of the total pool of GABA(B(1)) transcripts detected in ... More
Bioluminescence resonance energy transfer reveals the adrenocorticotropin (ACTH)-induced conformational change of the activated ACTH receptor complex in living cells.
AuthorsCooray SN, Chung TT, Mazhar K, Szidonya L, Clark AJ
JournalEndocrinology
PubMed ID21177829
The melanocortin 2 receptor (MC2R) accessory protein (MRAP) is a small single-transmembrane domain protein that plays a pivotal role in the function of the MC2R. The pituitary hormone, ACTH, acts via this receptor complex to stimulate adrenal steroidogenesis. Using both coimmunoprecipitation and bioluminescence resonance energy transfer (BRET), we show that ... More
A2A adenosine receptor (AR) activation inhibits pro-inflammatory cytokine production by human CD4+ helper T cells and regulates Helicobacter-induced gastritis and bacterial persistence.
AuthorsAlam MS, Kurtz CC, Wilson JM, Burnette BR, Wiznerowicz EB, Ross WG, Rieger JM, Figler RA, Linden J, Crowe SE, Ernst PB
JournalMucosal Immunol
PubMed ID19262506
Helicobacter pylori causes a lifelong infection and provides a model of bacterial adaptation and persistent colonization. Adenosine is an anti-inflammatory mediator that limits tissue damage during inflammation. We studied the role of adenosine in the T-cell-mediated regulation of gastritis and bacterial persistence. After 4 h of activation, human T helper ... More
Differential activation of "social" and "solitary" variants of the Caenorhabditis elegans G protein-coupled receptor NPR-1 by its cognate ligand AF9.
Natural variations of wild Caenorhabditis elegans isolates having either Phe-215 or Val-215 in NPR-1, a putative orphan neuropeptide Y-like G protein-coupled receptor, result in either "social" or "solitary" feeding behaviors (de Bono, M., and Bargmann, C. I. (1998) Cell 94, 679-689). We identified a nematode peptide, GLGPRPLRF-NH2 (AF9), as a ... More
Pharmacological inhibition of phosphodiesterase 4 triggers ovulation in follicle-stimulating hormone-primed rats.
AuthorsMcKenna SD, Pietropaolo M, Tos EG, Clark A, Fischer D, Kagan D, Bao B, Chedrese PJ, Palmer S
JournalEndocrinology
PubMed ID15448112
Phosphodiesterases (PDEs) are a family of enzymes that hydrolyze cyclic nucleotides to render them biologically inactive. As such, these enzymes are critical regulators of signal transduction pathways that use cyclic nucleotides as second messengers. PDE4 is one such member that has been identified in ovarian tissue and purported to have ... More
Pollen-derived E1-phytoprostanes signal via PPAR-gamma and NF-kappaB-dependent mechanisms.
AuthorsGilles S, Mariani V, Bryce M, Mueller MJ, Ring J, Jakob T, Pastore S, Behrendt H, Traidl-Hoffmann C
JournalJ Immunol
PubMed ID19454659
In a humid milieu such as mucosal surfaces, pollen grains do not only release allergens but also proinflammatory and immunomodulatory lipids, termed pollen-associated lipid mediators. Among these, the E(1)-phytoprostanes (PPE(1)) were identified to modulate dendritic cell (DC) function: PPE(1) inhibit the DC's capacity to produce IL-12 and enhance DC mediated ... More
Detection of G protein-coupled receptor-mediated cellular response involved in cytoskeletal rearrangement using surface plasmon resonance.
AuthorsChen K, Obinata H, Izumi T
JournalBiosens Bioelectron
PubMed ID20044245
G protein-coupled receptors (GPCRs) form a superfamily of cell surface receptors that play fundamental roles in physiology and pathophysiology. Although GPCRs have been the most successful targets for drug discovery, there still remain many orphan GPCRs, which provides opportunities for development of novel drugs. Here, we introduce a new method ... More
A calmodulin inhibitor, W-7 influences the effect of cyclic adenosine 3', 5'-monophosphate signaling on ligninolytic enzyme gene expression in Phanerochaete chrysosporium.
AuthorsSakamoto T, Yao Y, Hida Y, Honda Y, Watanabe T, Hashigaya W, Suzuki K, Irie T
JournalAMB Express
PubMed ID22273182
ABSTRACT: The capacity of white-rot fungi to degrade wood lignin may be highly applicable to the development of novel bioreactor systems, but the mechanisms underlying this function are not yet fully understood. Lignin peroxidase (LiP) and manganese peroxidase (MnP), which are thought to be very important for the ligninolytic property, ... More
An L-RNA-based aquaretic agent that inhibits vasopressin in vivo.
AuthorsPurschke WG, Eulberg D, Buchner K, Vonhoff S, Klussmann S
JournalProc Natl Acad Sci U S A
PubMed ID16547136
A class of diuretic/aquaretic agents based on mirror-image oligonucleotides (so-called Spiegelmers) has been identified. These molecules directly bind and inhibit the neuropeptide vasopressin (AVP). AVP is the major regulatory component of body fluid homeostasis mediated through binding to the renal V(2) receptor. Elevated plasma levels of AVP are implicated in ... More
Prostacyclin receptor suppresses cardiac fibrosis: role of CREB phosphorylation.
AuthorsChan EC, Dusting GJ, Guo N, Peshavariya HM, Taylor CJ, Dilley R, Narumiya S, Jiang F
JournalJ Mol Cell Cardiol
PubMed ID20403362
Cardiac fibrosis is a consequence of many cardiovascular diseases and contributes to impaired ventricular function. Activation of the prostacyclin receptor (IP) protects against cardiac fibrosis, but the molecular mechanisms are not totally understood. Using mouse cardiac fibroblasts, we found that IP activation with cicaprost suppressed expression of collagen I and ... More
Adrenergic receptor activation involves ATP release and feedback through purinergic receptors.
AuthorsSumi Y, Woehrle T, Chen Y, Yao Y, Li A, Junger WG
JournalAm J Physiol Cell Physiol
PubMed ID20668211
Formyl peptide receptor-induced chemotaxis of neutrophils depends on the release of ATP and autocrine feedback through purinergic receptors. Here, we show that adrenergic receptor signaling requires similar purinergic feedback mechanisms. Real-time RT-PCR analysis revealed that human embryonic kidney (HEK)-293 cells express several subtypes of adrenergic (a(1)-, a(2)-, and ß-receptors), adenosine ... More
Molecular determinants of melanocortin 4 receptor ligand binding and MC4/MC3 receptor selectivity.
AuthorsNickolls SA, Cismowski MI, Wang X, Wolff M, Conlon PJ, Maki RA
JournalJ Pharmacol Exp Ther
PubMed ID12604699
The molecular basis of ligand recognition by the melanocortin 4 receptor (MC4R) has not been fully defined. In this study, we investigated the molecular determinants of MC4R ligand binding, employing a large array of ligands, using three approaches. First, molecular modeling of the receptor was used to identify Phe284, in ... More
Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice.
AuthorsDing X, Saxena NK, Lin S, Gupta NA, Gupta N, Anania FA
JournalHepatology
PubMed ID16374859
Nonalcoholic fatty liver disease (NAFLD) represents a burgeoning problem in hepatology, and is associated with insulin resistance. Exendin-4 is a peptide agonist of the glucagon-like peptide (GLP) receptor that promotes insulin secretion. The aim of this study was to determine whether administration of Exendin-4 would reverse hepatic steatosis in ob/ob ... More
Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus.
AuthorsMarkus SM, Taneja SS, Logan SK, Li W, Ha S, Hittelman AB, Rogatsky I, Garabedian MJ
JournalMol Biol Cell
PubMed ID11854421
The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not ... More
Leptin transcriptionally enhances peptide transporter (hPepT1) expression and activity via the cAMP-response element-binding protein and Cdx2 transcription factors.
AuthorsNduati V, Yan Y, Dalmasso G, Driss A, Sitaraman S, Merlin D
JournalJ Biol Chem
PubMed ID16963449
PepT1 is an intestinal epithelial apical membrane transporter that is expressed in the small intestine, with little or no expression in the normal colon. However, we previously demonstrated that colonic PepT1 may be expressed during chronic inflammation. To begin elucidating inflammatory hPepT1 signaling, we herein investigated the long term leptin ... More
A prostacyclin receptor antagonist inhibits the sensitized release of substance P from rat sensory neurons.
AuthorsNakae K, Saito K, Iino T, Yamamoto N, Wakabayashi M, Yoshikawa S, Matsushima S, Miyashita H, Sugimoto H, Kiba A, Gupta J
JournalJ Pharmacol Exp Ther
PubMed ID16109742
Prostacyclin, one of the cyclooxygenase metabolites, causes various biological effects, including vasodilation and antithrombogenicity, and is also involved in several pathophysiological effects, such as inflammatory pain and bladder disorders. The prostacyclin receptor (IP receptor) agonists iloprost, cicaprost, and carbacyclin have been useful for clarifying the role of the IP receptor ... More
DiPOA ([8-(3,3-diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-acetic acid), a novel, systemically available, and peripherally restricted mu opioid agonist with antihyperalgesic activity: I. In vitro pharmacological characterization and pharmacokinetic properties.
AuthorsValenzano KJ, Miller W, Chen Z, Shan S, Crumley G, Victory SF, Davies E, Huang JC, Allie N, Nolan SJ, Rotshteyn Y, Kyle DJ, Broglé K
JournalJ Pharmacol Exp Ther
PubMed ID15054115
Mu opioid receptors are present throughout the central and peripheral nervous systems. Peripheral inflammation causes an increase in mu receptor levels on peripheral terminals of primary afferent neurons. Recent studies indicate that activation of peripheral mu receptors produces antihyperalgesic effects in animals and humans. Here, we describe the in vitro ... More
Rational design, synthesis, and structure-activity relationships of aryltriazoles as novel corticotropin-releasing factor-1 receptor antagonists.
AuthorsLowe RF, Nelson J, Dang TN, Crowe PD, Pahuja A, McCarthy JR, Grigoriadis DE, Conlon P, Saunders J, Chen C, Szabo T, Chen TK, Bozigian H
JournalJ Med Chem
PubMed ID15743196
Following the discovery of the very high binding affinity of 4-anilinopyrimidines against corticotropin-releasing factor receptor-1 (CRF(1)) (e.g., 1, K(i) = 2 nM), a new series of triazoles bearing different groups has been synthesized and evaluated. The compounds were prepared by cyclizations of N-acyl-S-methylisothioureas with alkylhydrazines or by cyclizations with hydrazine ... More
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation.
AuthorsWatanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J
JournalNature
PubMed ID16400329
While bile acids (BAs) have long been known to be essential in dietary lipid absorption and cholesterol catabolism, in recent years an important role for BAs as signalling molecules has emerged. BAs activate mitogen-activated protein kinase pathways, are ligands for the G-protein-coupled receptor (GPCR) TGR5 and activate nuclear hormone receptors ... More
A novel partial agonist of the A(1)-adenosine receptor and evidence of receptor homogeneity in adipocytes.
AuthorsFatholahi M, Xiang Y, Wu Y, Li Y, Wu L, Dhalla AK, Belardinelli L, Shryock JC
JournalJ Pharmacol Exp Ther
PubMed ID16410404
This study characterizes the receptor binding and functional effects of CVT-3619 [2-{6-[((1R,2R)-2-hydroxycyclopentyl)-amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2-fluorophenylthio)methyl]-oxolane-3,4-diol], a novel N(6)-5' -substituted adenosine analog and A(1) -adenosine receptor (A(1) AdoR) agonist, on rat epididymal and inguinal adipocytes and on the isolated heart and compares these effects with those caused by the full agonist N(6) -cyclopentyladenosine (CPA). ... More
Molecular interactions of nonpeptide agonists and antagonists with the melanocortin-4 receptor.
AuthorsFleck BA, Chen C, Yang W, Huntley R, Markison S, Nickolls SA, Foster AC, Hoare SR
JournalBiochemistry
PubMed ID16262250
The melanocortin-4 (MC4) receptor is a potential therapeutic target for obesity and cachexia, for which nonpeptide agonists and antagonists are being developed, respectively. The aim of this study was to identify molecular interactions between the MC4 receptor and nonpeptide ligands, and to compare the mechanism of binding between agonist and ... More
Agonist-induced polarized trafficking and surface expression of the adenosine 2b receptor in intestinal epithelial cells: role of SNARE proteins.
Adenosine, acting through the A2b receptor, induces vectorial chloride and IL-6 secretion in intestinal epithelia and may play an important role in intestinal inflammation. We have previously shown that apical or basolateral adenosine receptor stimulation results in the recruitment of the A2b receptor to the plasma membrane. In this study, ... More