Abstract:
:Complete nucleotide sequences are now available for different species of the animal kingdom: Caenorhabditis elegans - a nematode, Drosophila - an insect, and humans - a mammal. Such information makes it possible to compare the set of nuclear receptors found in these organisms, and to discuss the possible reasons for the differences observed. The human genome sequencing identified few new receptors, which implies that most nuclear receptors have now been found. However, information about polymorphisms and regulating sequences, obtained through genomic sequencing, will be important for understanding receptor function and disease mechanisms. The surprisingly large number of nuclear receptors in C. elegans might have implications for the development of pharmaceuticals and the understanding of the function of these animals. By contrast, Drosophila has few nuclear receptors; however, examination of the unique nuclear receptors provides information about the function of these receptors.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Enmark E,Gustafsson JAdoi
10.1016/s0165-6147(00)01859-9subject
Has Abstractpub_date
2001-12-01 00:00:00pages
611-5issue
12eissn
0165-6147issn
1873-3735pii
S0165-6147(00)01859-9journal_volume
22pub_type
杂志文章,评审abstract::Approximately 27 million people are living with a tumour in which the tumour suppressing activity of p53 has been inactivated. In half of these tumours, p53 itself is not mutated but the pathway is partially abrogated. Mechanisms include the overexpression of negative regulators of p53, such as MDM2 and MDM4, and dele...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2010.11.004
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abstract::For many years the prevailing view of how steroid hormone receptors exert their effects on gene transcription has been that these intracellular receptor proteins, upon association with their specific cognate ligands, undergo a transformation to a state where they are capable of interacting with chromatin and regulatin...
journal_title:Trends in pharmacological sciences
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doi:10.1016/0165-6147(92)90099-r
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01865-4
更新日期:2002-01-01 00:00:00
abstract::The therapeutic advantage of reducing the activity of interleukin 1 (IL-1) resides in preventing its deleterious biological effects without interfering with homeostasis. As such, methods attempting to block the production or activity of IL-1 have now entered clinical trials. For example, IL-1 induction of prostaglandi...
journal_title:Trends in pharmacological sciences
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更新日期:1993-05-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) comprise a large and diverse class of signal-transducing receptors that undergo dynamic and isoform-specific membrane trafficking. GPCRs thus have an inherent potential to initiate or regulate signaling reactions from multiple membrane locations. This review discusses emerging insig...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:2018-02-01 00:00:00
abstract::Drug development consumes huge amounts of time and money and the search for novel analgesics, which are urgently required, is particularly difficult, having resulted in many setbacks in the past. Drug repurposing - the identification of new uses for existing drugs - is an alternative approach, which bypasses most of t...
journal_title:Trends in pharmacological sciences
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abstract::Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs predominantly found in microorganisms. Increasing evidence supports a role for TLRs in sterile inflammation as observed in neurodegenerative disorders. This includes work suggesting a contribution for these receptors to t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:2012-10-01 00:00:00
abstract::In the discipline of pharmacology, drugs (ligands) are used as tools to elucidate the processes of biological systems. Because of this, pharmacologists strive to delineate all characteristics of drugs. Decades of research have resulted in the proposal that ligands possess two properties that are intrinsic to the ligan...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:1998-07-01 00:00:00
abstract::Folates are essential for key biosynthetic processes in mammalian cells and play a crucial role in the maintenance of central nervous system homeostasis. Mammals lack the metabolic capacity for folate biosynthesis; hence, folate requirements are largely met through dietary sources. To date, three major folate transpor...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2012.02.002
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:1998-05-01 00:00:00
abstract::Receptors, enzymes, and ion channels are traditional targets of therapeutic development. A common strategy is to target these proteins with agents that either activate or suppress their activity with ligands or substrates that occupy orthosteric sites or have allosteric interactions. An alternative approach involves r...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.05.004
更新日期:2015-08-01 00:00:00
abstract::The enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate species either to DNA synthesis or to homocysteine (Hcy) remethylation. The common MTHFR C677T polymorphism affects the activity of the enzyme and hence folate distribution. Under conditions of impaired folate status, the homozygous TT genotype has ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01675-8
更新日期:2001-04-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is an incurable disease that arises from the progressive loss of motoneurons. Even when caused by a single gene defect, as in the case of mutations in the enzyme Cu-Zn superoxide dismutase (SOD1), ALS is the result of a complex cascade that involves crosstalk among motoneurons, glia...
journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2006.03.009
更新日期:2006-05-01 00:00:00
abstract::Alanine-glyoxylate aminotransferase 2 (AGXT2) is a multifunctional mitochondrial aminotransferase that was first identified in 1978. The physiological importance of AGXT2 was largely overlooked for three decades because AGXT2 is less active in glyoxylate metabolism than AGXT1, the enzyme that is deficient in primary h...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:2014-11-01 00:00:00
abstract::The myeloid-derived suppressor cell (MDSC) is the 'queen bee' of the tumor microenvironment. MDSCs protect the cancer from the patient's immune system, make the tumor resistant to immunotherapy, and allow the tumor to thrive while the patient withers away. Eliminating MDSCs should improve response rates to cancer ther...
journal_title:Trends in pharmacological sciences
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更新日期:2019-01-01 00:00:00
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(91)90566-b
更新日期:1991-07-01 00:00:00
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:2003-06-01 00:00:00
abstract::Muscarinic acetylcholine receptor subtypes m1, m3 and m5 couple strongly to phosphatidylinositol turnover and hence to intracellular Ca2+ concentration via pertussis toxin (PTX) sensitive and insensitive G proteins. The m2 and m4 muscarinic receptor subtypes strongly inhibit adenylyl cyclase production via PTX sensiti...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:
更新日期:1989-12-01 00:00:00
abstract::Muscarinic agonists open potassium-selective K(ACh) channels in cardiac myocytes of pacemaker or atrial origin. Receptor activation is coupled to channel opening by a membrane bound guanine nucleotide-binding protein (GK) through a process that does not require cytoplasmic intermediates. We have used the muscarinic po...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:
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abstract::Steroid hormones are recognized as producing their major long-term effects on cell structure and function via intracellular receptors acting on the expression of genes. There is now increasing evidence that steroids also affect the surface of cells and alter ion permeability, as well as release of neurohormones and ne...
journal_title:Trends in pharmacological sciences
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abstract::Nuclear receptors represent a large class of ligand-activated transcriptional regulators; about 70 members of this protein family have been cloned from mammalian or insect species. Thus, it came as a great surprise when the recent completion of the Caenorhabditis elegans genome revealed at least 228 genes for nuclear ...
journal_title:Trends in pharmacological sciences
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abstract::Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective μ-opioid receptor agonist, but the...
journal_title:Trends in pharmacological sciences
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abstract::Biogenic amines and amino acids have been implicated in central cardiovascular homeostasis. Initially, drugs were injected into the brain and their effects on blood pressure were investigated. Other approaches allowed endogenous neurotransmitters released in the extracellular space of brain structures involved in card...
journal_title:Trends in pharmacological sciences
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更新日期:1996-10-01 00:00:00
abstract::Three 'alpha 1-adrenoceptors' and three 'alpha 2-adrenoceptors' have now been cloned. How closely do these receptors match the native receptors that have been identified pharmacologically? What are the properties of these receptors, and how do they relate to other members of the cationic amine receptor family? Kevin L...
journal_title:Trends in pharmacological sciences
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更新日期:1991-02-01 00:00:00
abstract::Seven-transmembrane receptors are prototypic allosteric proteins with the ability to adopt numerous conformations, many of which interact with cellular partners to initiate cellular biochemical processes. Defining efficacy as the ability of ligands to stabilize some of these conformations (which, in turn, possess phys...
journal_title:Trends in pharmacological sciences
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更新日期:2007-08-01 00:00:00
abstract::B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a br...
journal_title:Trends in pharmacological sciences
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abstract::Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in...
journal_title:Trends in pharmacological sciences
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abstract::Adenosine is an endogenous nucleoside that modulates many physiological processes. Its actions are mediated by interaction with specific cell membrane receptors. Four subtypes of adenosine receptor have been cloned: A1, A2A, A2B and A3. Significant advancement has been made in our understanding of the molecular pharma...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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abstract::Antipsychotic drugs (APDs), and the 'atypical' APDs in particular, are commonly associated with metabolic side effects in humans. These include glucose dysregulation, insulin resistance, hyperlipidemia, weight gain and hypertension, which put patients at increased risk of cardiometabolic disorders. The underlying biol...
journal_title:Trends in pharmacological sciences
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doi:10.1016/j.tips.2010.07.002
更新日期:2010-10-01 00:00:00