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
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
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
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
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