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Topic: Orphan receptor

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	Opioid Receptors
		receptor was accepted as a member of the "family" of opioid receptors on the basis of its structural homology towards the classical types, there is no corresponding pharmacological homology.
		However, different responses evoked in different cell types in response to activation of different opioid receptors or even in response to activation of the same receptor are likely to reflect changes in the expression of G proteins and effector systems between cell types rather than any inherent differences in the properties of the receptors themselves.
		Among the receptors for the many neuropeptides that exist in the nervous system, the opioid receptors are unique in that there existed before the discovery of the natural agonists, an abundance of non-peptide ligands with which the pharmacology of the receptors was already defined.
	opioids.com /receptors (5011 words)

	Opioid receptor - Wikipedia, the free encyclopedia (Site not responding. Last check: 2007-10-01)
		The receptors were named using the first letter of the first ligand that was found to bind to them.
		Similarly a drug known as Ketocyclazocine was first shown to attach itself to kappa receptors [1].An alternative classification system is based on their order of discovery the receptors being termed OP (κ), and OP The opioid receptor types are ~70% identical with differences located at N and C termini.
		However, pharmacological testing indicated that the sigma receptors were activated by drugs completely unrelated to the opioids, and their function was unrelated to the function of the opioid receptors.
	www.marijuana.com /wiki/Opioid_receptor (945 words)

	NR4A1 - nuclear receptor subfamily 4, group A, member 1
		Nur77 and its related receptors were shown to be important mediators for control of apoptosis induced by the T-cell receptor, and they also mediate the effect of the hypothalamic hormone CRH on transcription of the pituitary pro-opiomelanocotin (POMC) gene.
		During T cell receptor activation, HDAC7 is exported from the nucleus leading to the derepression of Nur77 expression and the induction of apoptosis.
		The aim of this study was to investigate the role of HBx in expression of Nur77, an orphan nuclear receptor implicated in the upregulation of FasL.
	www.pdg.cnb.uam.es /UniPub/iHOP/gg/89073.html (6881 words)

	Researchers Identify Mechanism That May Regulate Protein Involved In Sex Differentiation, Stress, Hunger
		The small-molecule hormones, or "ligands," that regulate most of these nuclear receptors sweep into a cell's nucleus from far-flung cells and latch on to their respective receptor, prompting it to bind with nearby molecular "co-factors." Together, the receptor and its co-factors bring about the change in a given gene's behavior.
		The molecule, or ligand, that signals the SF-1 nuclear receptor to prompt a change in gene activity has been elusive, however, leading to its designation as an "orphan" receptor, and leaving researchers suspicious that some signal other than a small-molecule hormone might be orchestrating its actions.
		The researchers determined that the SF-1 receptor is regulated by a cascade of signals initiated outside of the cell that, through a series of molecular events, ultimately cause a change in the molecular makeup of the receptor in the nucleus.
	www.eurekalert.org /pub_releases/1999-04/UoCS-RIMT-260499.php (1041 words)

	Dr Janet Maguire
		We have investigated ET receptor expression in human atherosclerotic coronary artery and diseased saphenous vein bypass grafts retrieved from explanted hearts and correlated this to functional changes.
		We have discovered that medial ET receptors are not up-regulated in disease, as proposed from animal studies, and excessive vasospasm in these conditions is due to activation of the ET receptor.
		receptors are not down-regulated in response to increased circulating ET-1.
	www-davenport.medschl.cam.ac.uk /maguire.html (811 words)

	PENCE (Site not responding. Last check: 2007-10-01)
		The TrkA receptor agonists are being used as leads to develop small molecule ligands that activate the receptor, and could be useful in Alzheimer's disease and in pain management.
		This receptor is involved in the regulation of lymphocyte proliferation and in neural differentiation.
		A cell cycle regulating receptor is localized on the cell surface and in the nuclei of mitotically and meiotically proliferating cells.
	www.pence.ca /pence/en/index.php?bios/h_saragovi (923 words)

	TNFSF14 - tumor necrosis factor (ligand) superfamily, member 14
		Comparison of the amino acid sequence of mTR2R1 with other nuclear receptors indicates that it is most closely related to the orphan receptor, hTR2, and suggests that these proteins constitute a novel subfamily within the nuclear receptor superfamily.
		p53 is a mediator for radiation- repressed human TR2 orphan receptor expression in MCF-7 cells, a new pathway from tumor suppressor to member of the steroid receptor superfamily.
		Receptor binding residues via LIGHT were identified by introducing point mutations in the A' --> A" and D --> E loops of LIGHT, which altered binding to LTbetaR and HveA.
	www.pdg.cnb.uam.es /UniPub/iHOP/gg/94102.html (2088 words)

	Nepkar
		Receptor targets are membrane-spanning proteins which connect the inside of cells to the outside.
		The functional interaction of a receptor with the internal signaling machinery of a cell, allowing the receptor to work.
		Receptor protein, typically identified from genomic sequencing, for which the natural ligand is unknown.
	www.businessplans.org /Nepkar/Nepka00.html (1175 words)

	Newswise
		The scientists found the receptor through a laborious technique known as an "orphan receptor strategy," in which receptors are tested to see if they bind against neurotransmitters, hormones and other chemicals, much like bait is used to catch a fish.
		Receptors also can act as a gateway between blood vessels and nerve cells, binding with chemicals in the body that in turn stimulate nerve cells to constrict or loosen blood vessels.
		Recently, Civelli and his colleagues found a receptor that plays a role in regulating eating behavior and could be used to design drugs that fight obesity, and a receptor that appears to help the body regulate its reactions to stress.
	www.newswise.com /articles/view?id=PRESSURE.UCI (750 words)

	ORPHAN NUCLEAR RECEPTORSBiology and Ligand Identification
		The nuclear receptors PPAR and LXR regulate macrophage gene expression in response to oxidized lipids.
		These orphan receptors not only provide opportunities to characterize novel signal transduction pathways but also may be new potential drug targets.
		Orphan nuclear receptors (NRs) are the most abundant transcriptional regulators encoded in the genome of the free-living nematode Caenorhabditis elegans, with >250 predicted NR genes.
	www.knowledgefoundation.com /events/1121302.htm (3125 words)

	DAYBREAK - Researchers Discover New Immune System Molecule
		Although its association with a chemokine was a discovery, the receptor turned out to be one that had already been isolated by other researchers in cell studies as one of the receptors exploited by invading HIV viruses to gain entry into human cells.
		Cytotoxic CD8 T cells, known for the ability to kill virally infected cells, were found to express the chemokine receptor and to be able to migrate towards a source of the chemokine.
		In addition to CD8 T cells, the receptor was found on subpopulations of CD4 T cells, including a specialized population of CD4 T cells that live in the gut and that are known as intra-epithelial T cells.
	www.ucsf.edu /daybreak/2000/10/09_immune.htm (677 words)

	NURSA \| Nuclear Receptor Signaling Atlas \| Receptors, Coactivators, Corepressors and Ligands
		A fundamental goal of orphan receptor research is the identification of ligands for these receptors.
		Among the mammalian orphan receptors there remain approximately 26 that not have been clearly associated with a corresponding ligand from mammalian tissues.
		Moreover, for the vast majority of the 11 receptors that have been linked to naturally occurring compounds, there is no consensus as to the identity of the true endogenous ligand.
	www.nursa.org /template.cfm?threadId=359 (477 words)

	Barry Forman, MD (Site not responding. Last check: 2007-10-01)
		Nuclear hormone receptors comprise a super-family of ligand-activated transcription factors that mediate the biological effects of steroid, retinoid and thyroid hormones.
		After nuclear receptors had been isolated for all known nuclear-acting hormones, a large group of additional receptor-like proteins were identified.
		These proteins are known as orphan receptors as they appear to represent receptors for yet-to-be discovered ligands.
	www.cityofhope.org /Diabetes/Team/BarryForman.htm (634 words)

	Lund University, Doctoral Dissertation (Site not responding. Last check: 2007-10-01)
		Orphan receptors were selected using known receptor sequences as templates and subsequently cloned into expressing plasmids that were then stably transfected into luciferase-based reporter cells.
		An orphan receptor was found to be the second GPCR, BLT2, activated by the pro-inflammatory molecule leukotriene B4.
		Through use of a library of orphan receptors, potential ligands were screened for activity by applying reversed pharmacology.
	www.lub.lu.se /cgi-bin/show_diss.pl/med_906.html (942 words)

	Discovery Of A Molecule That Controls Bile Acids May Lead To New Cholesterol Drugs
		Their finding -- that the receptor FXR (farnesoid orphan receptor) is integral to maintaining the balance of cholesterol and bile acids -- has important implications for developing drugs to control dietary cholesterol in humans, said corresponding author of the study Dr. David Mangelsdorf, associate professor of pharmacology and Howard Hughes Medical Institute (HHMI) investigator.
		These substances activate liver orphan receptor (LXR) to speed up the breakdown of cholesterol for conversion to bile acids and steroid hormones.
		Orphan receptors are molecules believed to be the locks that control biochemical processes but whose function and ligand, or key, to activate the cellular changes, is unknown.
	www.eurekalert.org /pub_releases/1999-05/UoTS-DOAM-210599.php (497 words)

	Genome Biology \| Abstract \| Phylogenetic analysis of 277 human G-protein-coupled receptors as a tool for the prediction ...
		We hypothesized that a more complete knowledge of the phylogenetic relationship of these orphan receptors to receptors with known ligands could facilitate ligand identification, as related receptors often have ligands with similar structural features.
		A database search excluding olfactory and gustatory receptors was used to compile a list of accession numbers and synonyms of 81 orphan and 196 human GPCRs with known ligands.
		This approach may prove valuable for identification of the natural ligands of orphan receptors as their relation to receptors with known ligands becomes more evident.
	www.genomebiology.com /2002/3/11/research/0063/abstract (331 words)

	The Nuclear Orphan Receptor TR4 Promotes Proliferation of Myeloid Progenitor Cells -- Koritschoner et al. 12 (11): 563 ...
		The Nuclear Orphan Receptor TR4 Promotes Proliferation of Myeloid Progenitor Cells -- Koritschoner et al.
		The Nuclear Orphan Receptor TR4 Promotes Proliferation of Myeloid Progenitor Cells
		the orphan receptor TR4 as an important regulator of myeloid
	cgd.aacrjournals.org /cgi/content/abstract/12/11/563 (335 words)

	U of M: Pharmacology: Faculty: Wei.
		Vitamin A exerts a variety of effects on biological systems and its action is mediated through various intracellular receptors that ultimately lead to changes in gene expression.
		The focus of the first project is to examine the roles of nuclear retinoic acid receptors in vitamin A action by using both transgenic mouse and embryonal carcinoma cell culture systems.
		The focus of the second project is to understand the mechanism of opioid receptor gene expression, including transcriptional control, RNA processing and translation efficiency.
	www.pharmacology.med.umn.edu /staffwei.html (573 words)

	Dr. Mangelsdorf , Dr. David Mangelsdorf, Dr. David John Mangelsdorf
		These receptors orchestrate the body?s response to a myriad of crucial hormones, which include the steroid hormones, thyroid hormone, and vitamins D and A. His interest in this field began as a graduate student, where his research on vitamin D resulted in the cloning of the vitamin D receptor.
		This was the first ligand to be discovered for an orphan nuclear receptor and this finding ushered in the era of orphan receptor research.
		More recently, his laboratory discovered ligands for the C. elegans nuclear receptor, DAF-12, which are the first hormonal ligands for an invertebrate orphan receptor to be discovered.
	www8.utsouthwestern.edu /findfac/personal/0,2358,14570,00.html (433 words)

	[No title]
		Steroid or nuclear hormone receptors (4A nuclear receptor, NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis.
		In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.
		Novel members of the steroid receptor superfamily designated NOR-1 (neuron derived orphan receptor) [4], Nurr1 (Nur-related factor 1) [5], and NGFI-B [6] have been identified from forebrain neuronal cells undergoing apoptosis, from brain cortex, and from lung, superior cervical ganglia and adrenal tissue respectively.
	www.ebi.ac.uk /interpro/IEntry?ac=IPR003070 (897 words)

	CART : Arena Pharmaceuticals (Site not responding. Last check: 2007-10-01)
		When the receptor’s natural ligand binds to the “loops” of a GPCR that are located on the outside of the cell surface, an interior “loop” is moved further down within the cell, and this allows a G protein to couple to this portion of the receptor.
		For traditional, ligand-based drug discovery, scientists screen for small molecules that are intended to interact with the outside loops of the receptor at or near where the receptor’s ligand binds, generally to block the ligand from binding to the receptor.
		Because CART does not require the receptor’s natural ligand to produce a signal, screening using a CART-activated receptor is not limited to finding small molecules that only bind to the site on the receptor where the ligand binds.
	www.arenapharm.com /wt/page/cart (970 words)

	Vishva M. Dixit (Site not responding. Last check: 2007-10-01)
		Members of the tumor necrosis factor receptor (TNFR) family are related to each other in possessing extracellular cysteine-rich domains.
		A subset of these receptors share a cytoplasmic "death domain," a protein-protein interaction motif critical for engaging downstream components of the signal transduction machinery.
		This receptor is highly expressed on thymocytes and lymphocytes and is likely to play a significant role in immune function.
	www.cancerresearch.org /cancervaccines2000/vishva_dixit.html (292 words)

	Nuclear Receptors: Key Targets for New Pharmaceuticals
		Nuclear receptors are a family of proteins involved in key metabolic processes with great potential as targets for the treatment of significant diseases such as cancer, coronary heart disease, and diabetes.
		Nuclear receptors are attractive targets for drug discovery because those that have been discovered thus far have proved to be "druggable", in other words, their activity can be modulated by small molecules.
		Gain an understanding of nuclear receptor controlled pathways and how the modulation of these pathways forms a target for rational drug design with an overview of what is known about each receptor and how they impact disease processes.
	www.bioportfolio.com /reports/DMD_Nuclear_Receptors.htm (513 words)

	Genome Biology \| Full text \| Genomic structure of the gene for mouse germ cell nuclear factor (GCNF)
		The germ cell nuclear factor (GCNF, also known as retinoid acid receptor-related testis-associated receptor, neuronal cell nuclear receptor or NR6A1) is an orphan receptor in the nuclear receptor superfamily found in mammals, amphibians and fish.
		Also known as RTR (retinoid acid receptor-related testis-associated receptor) or NCNF (neuronal cell nuclear receptor), evolutionary studies have defined GCNF as the only known member of a sixth subfamily of nuclear receptors [7,8,9].
		Laudet V: Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor.
	www.genomebiology.com /2000/1/3/research/0006 (1340 words)

	Tramadol, buy tramadol, antibiotics, Weight Loss drugs, weight loss herbs, weight loss herbal formula, weight loss, ... (Site not responding. Last check: 2007-10-01)
		Decreased phorbol ester receptor and protein kinase C in P388 murine leukemic cells resistant to etoposide.
		The activity of protein kinase C, which is related to the phorbol ester receptor, significantly decreased in the variant cell.
		The aim of this study was to assess the prognostic role of soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete remission (CR) and in predicting disease relapse.
	www.wellstreetpharmacy.com /ref-condylox/condylox-research-abs3.1419.html (794 words)

	Finding the Needle in a Haystack: Thrombopoeitin
		It appeared to be a growth factor receptor related to blood cells.
		Competitors had cloned the receptor and fashioned a sort of molecular "filter" out of it: They attached many of the receptors to the surfaces inside a tube, and then passed blood through the tube, with the strategy that the receptors would "catch"and concentrate TPO molecules as the blood passed by.
		They took a type of mouse leukemia cell that grows only if it is stimulated by hormones, and they engineered it so that the hormone it would respond to is the hormone that binds to the orphan receptor.
	www.washington.edu /research/pathbreakers/1994b.html (665 words)

	BCM - Developmental Biology - Sophia Y. Tsai
		Our research focuses on two main areas: the first is to examine the physiological role of nuclear orphan receptor COUP-TFII in mouse development.
		Currently, we are using three transgenic models, to induce expression of either int-2, AIB-1 or Cdc25B, to investigate the interaction of oncogenes and hormones in the transformation of the mammary gland epithelium.
		Zhou C, Qiu Y, Pereira FA, Crair MC, Tsai SY, Tsai MJ (1999) The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons.
	www.bcm.edu /db/db_fac-tsais.html (507 words)

	Orphan Receptor Ligand Discovery
		14TM have in-house phylognetic analysis methods and tools that can identify the ligand for any orphan receptors - the process is significantly more accurate that other methods which can give eroneous results.
		Lead compounds are curently being tested against each of these receptors for confirmation of biological activty.
		The fact that that many of these receptors bind "inforamtion poor" natural ligands such as free fatty acids makes ligand based discovery extremely difficult.The structure based approach used by 14TM and Proteom enables hits to be identified without prior knowledge of ligands.
	www.14tm.com /orphans.htm (109 words)

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