New drug binding sites in Ca2+ channels.

abstract：:Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanisti...

journal_title：Trends in pharmacological sciences

authors： Cahill CM,Walwyn W,Taylor AMW,Pradhan AAA,Evans CJ

更新日期：2016-11-01 00:00:00

abstract：:The potent pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1) are capable of triggering biologically similar effects through activation of the same set of transcription factors. Based on recent findings it is now becoming evident that certain members of the mitogen-activated p...

journal_title：Trends in pharmacological sciences

authors： Eder J

更新日期：1997-09-01 00:00:00

abstract：:The vascular system is rich in G-protein-coupled receptors (GPCRs), particularly Class 1 GPCRs, which are activated by an eclectic range of chemical entities including peptides. These chemical messengers can function in blood vessels as directly acting vasoconstrictors, directly acting vasodilators or indirectly actin...

journal_title：Trends in pharmacological sciences

authors： Maguire JJ,Davenport AP

更新日期：2005-09-01 00:00:00

abstract：:Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice wit...

journal_title：Trends in pharmacological sciences

authors： Leslie NR,Foti M

更新日期：2011-03-01 00:00:00

abstract：:Progress in understanding the genetic changes that drive tumorigenesis has enabled the development of molecularly targeted anticancer therapy. The first small molecule targeted to a specific protein was imatinib mesylate (Gleevec, STI571), which is used to treat chronic myeloid leukemia (CML). A recent article present...

journal_title：Trends in pharmacological sciences

authors： Michor F

更新日期：2007-05-01 00:00:00

abstract：:The efficacy of the powerful CRISPR-Cas9 genome-editing platform depends on DNA repair activities in the cells being targeted. Two new papers show that the low efficiency of targeting in some primary human cell lines is the result of p53-dependent cell arrest in response to the Cas9-induced break. This limitation must...

journal_title：Trends in pharmacological sciences

authors： Carroll D

更新日期：2018-09-01 00:00:00

abstract：:The 5-hydroxytryptamine (5-HT)(2C) receptor has received considerable attention as a target for treating drug addiction. 5-HT(2C)-receptor agonism, however, also induces side-effects. In this article, we review recent findings regarding the involvement of 5-HT(2C) receptors in behaviours related to drug addiction in a...

journal_title：Trends in pharmacological sciences

authors： Müller CP,Carey RJ

更新日期：2006-09-01 00:00:00

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

authors： Ma'ayan A,Rouillard AD,Clark NR,Wang Z,Duan Q,Kou Y

更新日期：2014-09-01 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

authors： Rodionov RN,Jarzebska N,Weiss N,Lentz SR

更新日期：2014-11-01 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

authors： Clarke WP,Bond RA

更新日期：1998-07-01 00:00:00

abstract：:A family of peptides that shares a common C-terminal sequence (Phe-X-Gly-Leu-MetNH2) exists in mammalian and non-mammalian species. In mammals, three of these peptides (substance P, neurokinin A and neurokinin B) satisfy the criteria to be considered as neurotransmitters either in the central, peripheral or enteric ne...

journal_title：Trends in pharmacological sciences

authors： Maggi CA

更新日期：2000-05-01 00:00:00

abstract：:Benzodiazepines in clinical use have a range of pharmacological activities. Some, e.g. sedation, tolerance and addiction, are not welcome. Undesirable side-effects of drugs are often controlled by developing compounds that bind more selectively to one particular receptor subtype. An alternative approach, discussed her...

journal_title：Trends in pharmacological sciences

authors： Haefely W,Martin JR,Schoch P

更新日期：1990-11-01 00:00:00

abstract：:Epoxyeicosatrienoic acids (EETs), derived from arachidonic acid by cytochrome P450 epoxygenases, are potent vasodilators that function as endothelium-derived hyperpolarizing factors in some vascular beds. EETs are rapidly metabolized by soluble epoxide hydrolase to form dihydroxyeicosatrienoic acids (DHETs). Recent re...

journal_title：Trends in pharmacological sciences

authors： Larsen BT,Campbell WB,Gutterman DD

更新日期：2007-01-01 00:00:00

abstract：:Schizophrenia is a grave psychiatric disorder with psychotic symptoms and an enigmatic etiology. Family studies have strongly indicated that genetic risk factors have a role in this disease. Recent findings, together with previously established evidence, highlight the PDZ-domain-containing protein interacting with C-k...

journal_title：Trends in pharmacological sciences

authors： Dev KK,Henley JM

更新日期：2006-11-01 00:00:00

abstract：:Within five years of discovering endothelin (ET-1) in 1988, the first report of an orally available ET receptor antagonist was published. Within twelve years, bosentan, the first ET receptor antagonist to gain marketing authorization, was made available for the treatment of pulmonary artery hypertension (PAH). Since t...

journal_title：Trends in pharmacological sciences

authors： Dhaun N,Pollock DM,Goddard J,Webb DJ

更新日期：2007-11-01 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

authors： Ueland PM,Hustad S,Schneede J,Refsum H,Vollset SE

更新日期：2001-04-01 00:00:00

abstract：:It has been hypothesized that anxiety disorders play an important role in the initiation and maintenance of alcohol drinking behaviors. However, the molecular mechanisms for the association between anxiety and alcohol abuse are not well understood. Structures of the extended amygdala, particularly the central nucleus ...

journal_title：Trends in pharmacological sciences

authors： Pandey SC

更新日期：2003-09-01 00:00:00

abstract：:During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial ce...

journal_title：Trends in pharmacological sciences

authors： Guilarte TR,Loth MK,Guariglia SR

更新日期：2016-05-01 00:00:00

abstract：:Plants have been the predominant source of medicines throughout the vast majority of human history, and remain so today outside of industrialized societies. One of the most versatile in terms of its phytochemistry is cannabis, whose investigation has led directly to the discovery of a unique and widespread homeostatic...

journal_title：Trends in pharmacological sciences

authors： Russo EB

更新日期：2016-07-01 00:00:00

abstract：:Conus venoms from marine cone snails continue to provide novel bioactive components. Two new classes of conopeptide specifically block alpha(1)-adrenoceptors (rho-conopeptide) and noradrenaline transporters (chi-conopeptides). Both classes are small peptides with two disulfide bonds. Rho-conopeptide is structurally si...

journal_title：Trends in pharmacological sciences

authors： Harvey AL

更新日期：2002-05-01 00:00:00

abstract：:It is generally accepted that muscle wasting is caused by an increase in protein breakdown which seems to be associated with an ATP-dependent, non-lysosomal proteolytic system based on conjugation of proteins to the small polypeptide ubiquitin. Increases in ubiquitin conjugates and in ubiquitin mRNAs are found in the ...

journal_title：Trends in pharmacological sciences

authors： Argilés JM,López-Soriano FJ

更新日期：1996-06-01 00:00:00

abstract：:Much regarding the engagement of the G(12) family of heterotrimeric G proteins (G(12) and G(13)) by agonist-activated receptors remains unclear. For example, the identity of receptors that couple unequivocally to G(12) and G(13) and how signals are allocated among these and other G proteins remain open questions. Part...

journal_title：Trends in pharmacological sciences

authors： Riobo NA,Manning DR

更新日期：2005-03-01 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

authors： Carrì MT,Grignaschi G,Bendotti C

更新日期：2006-05-01 00:00:00

abstract：:Enveloped viruses pose an important health threat because most of the persistent and many emerging viruses are enveloped. In particular, newly emerging viruses create a need to develop broad-spectrum antivirals, which usually are obtained by targeting host cell factors. Persistent viruses have developed efficient stra...

journal_title：Trends in pharmacological sciences

authors： Wisskirchen K,Lucifora J,Michler T,Protzer U

更新日期：2014-09-01 00:00:00

abstract：:Recently, nicotinic acid adenine dinucleotide phosphate (NAADP) has been shown, using different techniques, to mobilize intracellular Ca2+ stores in invertebrate, lower vertebrate, plant and mammalian cells. This endogenous molecule might play an atypical role in Ca2+ signalling by coordinating the responses of other ...

journal_title：Trends in pharmacological sciences

authors： Genazzani AA,Billington RA

更新日期：2002-04-01 00:00:00

abstract：:Network and systems biology offer a novel way of approaching drug discovery by developing models that consider the global physiological environment of protein targets, and the effects of modifying them, without losing the key molecular details. Here we review some recent advances in network and systems biology applied...

journal_title：Trends in pharmacological sciences

authors： Pujol A,Mosca R,Farrés J,Aloy P

更新日期：2010-03-01 00:00:00

abstract：:Prospecting the full biodiversity of nature to find leads for new drugs is not necessary. Because finding leads is aimed at identifying biological activity, structure is of secondary importance. Furthermore, although natural chemical diversity might be unrivalled, functional diversity is bound to be considerably less....

journal_title：Trends in pharmacological sciences

authors： Tulp M,Bohlin L

更新日期：2002-05-01 00:00:00

abstract：:Clinical implementation of two recently approved antisense RNA therapeutics - Exondys51® to treat Duchenne muscular dystrophy (Duchenne MD) and Spinraza® as a treatment for spinal muscular atrophy (SMA) - highlights the therapeutic potential of antisense oligonucleotides (ASOs). As shown in the Duchenne and Becker cas...

journal_title：Trends in pharmacological sciences

authors： Li D,Mastaglia FL,Fletcher S,Wilton SD

更新日期：2018-11-01 00:00:00

abstract：:Opioid receptors are expressed on peripheral sensory nerve endings, cutaneous cells, and immune cells; and local application of opioids is used for the treatment of inflammatory pain in arthritis, burns, skin grafts, and chronic wounds. However, peripherally active opioids can also directly modulate the inflammatory p...

journal_title：Trends in pharmacological sciences

authors： Stein C,Küchler S

更新日期：2013-06-01 00:00:00

abstract：:Within the past six months, isolation of cDNA or genomic clones has been reported for three 5-HT receptors, the 5-HT1C, 5-HT1A and 5-HT2 subtypes. As members of the G protein receptor superfamily, all three 5-HT receptor clones encode single-subunit proteins containing approximately 450 amino acids arrayed as seven in...

journal_title：Trends in pharmacological sciences

authors： Hartig PR

更新日期：1989-02-01 00:00:00