Abstract：
:The discovery of neuropeptides as signaling molecules with paracrine or hormonal regulatory functions has led to trailblazing advances in physiology and fostered the characterization of numerous neuropeptide-binding G protein-coupled receptors (GPCRs) as potential drug targets. The impact on human health has been tremendous: approximately 30% of commercial drugs act via the GPCR pathway. However, about 25% of the GPCRs encoded by the mammalian genome still lack their pharmacological identity. Searching for the orphan GPCR endogenous ligands that are likely to be neuropeptides has proved to be a formidable task. Here we describe the mass spectrometry (MS)-based technologies and experimental strategies that have been successful in achieving high-throughput characterization of endogenous peptides in nervous and endocrine systems.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Romanova EV,Sweedler JVdoi
10.1016/j.tips.2015.05.009subject
Has Abstractpub_date
2015-09-01 00:00:00pages
579-86issue
9eissn
0165-6147issn
1873-3735pii
S0165-6147(15)00115-7journal_volume
36pub_type
杂志文章,评审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
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.04.005
更新日期：2016-07-01 00:00:00
abstract：:Bioluminescence resonance energy transfer has developed in recent years as a new technique to study protein-protein interactions. Protein partners of interest are tagged with either luciferase or green fluorescent protein (GFP). Non-radiative energy transfer between the excited luciferase and the GFP permits the study...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(02)02062-x
更新日期：2002-08-01 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：:Histamine-containing neurons and histamine H1 receptors are distributed within the brain and peripheral tissues. The results of physiological and pharmacological studies have revealed that brain histamine and H1 receptors are involved in the regulation of feeding and obesity in rodents. The adipocytokine leptin regula...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.03.008
更新日期：2006-05-01 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
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01990-8
更新日期：2002-04-01 00:00:00
abstract：:Humans are exposed to mixtures of chemicals, rather than to individual chemicals. From a public health point of view, it is most relevant to answer the question of whether or not the components in a mixture interact in a way that results in an increase in their overall effect compared with the sum of the effects of th...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01720-x
更新日期：2001-06-01 00:00:00
abstract：:Docking is now routine in virtual screening or lead optimization for drug screening and design. The number of papers related to docking has dramatically increased over the past decade. However, there are many issues to consider when undertaking a docking study. Frequent problems or issues arise, such as the wrong bind...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.12.001
更新日期：2015-02-01 00:00:00
abstract：:Successful biologics must satisfy multiple properties including activity and particular physicochemical features that are globally defined as developability. These multiple properties must be simultaneously optimized in a very broad design space of protein sequences and buffer compositions. In this context, artificial...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2020.12.004
更新日期：2021-01-23 00:00:00
abstract：:Apoptosis is an area of intense scientific interest, which encompasses the study of and triggers mechanisms involved in mediating the cell biology of programmed cell death. A number of low molecular weight compounds have been used to inhibit or enhance this fundamental cellular process and so apoptosis has now become ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01277-2
更新日期：1999-01-01 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
doi：10.1016/j.tips.2014.09.005
更新日期：2014-11-01 00:00:00
abstract：:Therapeutic targeting of the processes that regulate histone modification is a growing area of scientific exploration. Although most interest has concentrated on the various families of enzymes that contribute to these processes, this review focuses on emerging data demonstrating the chemical tractability and therapeu...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2011.12.002
更新日期：2012-03-01 00:00:00
abstract：:Clodronate is a first-generation bisphosphonate used worldwide for antiresorptive therapy for osteoporosis. Although clodronate is analgesic in nature, its mechanism and efficacy were unknown for some time. Recently, clodronate was identified as a selective and potent inhibitor for vesicular nucleotide transporter (VN...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2017.10.007
更新日期：2018-01-01 00:00:00
abstract：:The pursuit for drugs that inhibit cyclin-dependent kinases (CDKs) has been an intense area of research for more than 15 years. The first-generation inhibitors, Flavopiridol and CY-202, are in late-stage clinical trials, but so far have demonstrated only modest activity. Several second-generation inhibitors are now in...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2007.10.012
更新日期：2008-01-01 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
pub_type： 杂志文章
doi：10.1016/j.tips.2013.03.006
更新日期：2013-06-01 00:00:00
abstract：:Insect nicotinic acetylcholine (nACh) receptors are molecular targets of insecticides such as neonicotinoids that are used to control disease-carrying insects and agricultural pests. To date, several insect nACh receptor subunits have been identified, indicating different nACh receptor subtypes and pharmacological pro...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.11.006
更新日期：2007-01-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.12.005
更新日期：2011-03-01 00:00:00
abstract：:Neuromodulin is a neurospecific calmodulin binding protein that is implicated in neurite extension, axonal elongation and long-term potentiation. Yuechueng Liu and Daniel Storm propose that neuromodulin binds and concentrates calmodulin on growth cone membranes and that stimulation of protein kinase C releases high lo...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(90)90195-e
更新日期：1990-03-01 00:00:00
abstract：:Discoidin (DS) domains are found in eukaryotic and prokaryotic extracellular and transmembrane multidomain proteins. These small domains play different functional roles and can interact with phospholipids, glycans, and proteins, including collagens. DS domain-containing proteins are often involved in cellular adhesion...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.06.003
更新日期：2016-08-01 00:00:00
abstract：:From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one o...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2010.08.006
更新日期：2010-12-01 00:00:00
abstract：:Signal transducer and activator of transcription 3 (STAT3) plays crucial roles in several cellular processes such as cell proliferation and survival, and has been found to be aberrantly activated in many cancers. Much research has explored the leading mechanisms for regulating the STAT3 pathway and its role in promoti...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2015.10.001
更新日期：2016-01-01 00:00:00
abstract：:Pharmacology training in Canada was initiated at McGill University in Montréal in 1824, and there are now 17 pharmacology departments in Canada offering graduate training to more than 500 students. In this article, Gerald Marks reviews the growth of pharmacology in Canada since the early 19th century in both academic ...
journal_title：Trends in pharmacological sciences
pub_type： 历史文章,杂志文章
doi：10.1016/0165-6147(94)90312-3
更新日期：1994-07-01 00:00:00
abstract：:cGMP inhibits hypertrophy, decreases fibrosis, and protects against cardiac ischemia-reperfusion (I/R) injury. Gene-targeting studies have not defined a clear role for its major downstream effector, cGMP-dependent protein kinase I (cGKI), in cardiac hypertrophy, but do implicate cGMP-cGKI signaling in fibrosis and I/R...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.05.003
更新日期：2014-08-01 00:00:00
abstract：:The tachykinin family has recently been extended by the discovery of a third tachykinin gene encoding previously unknown mammalian tachykinins (hemokinin 1, endokinin A and endokinin B) that have a widespread peripheral distribution and a tachykinin NK(1) receptor selectivity. This and the identification of other tach...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2003.11.005
更新日期：2004-01-01 00:00:00
abstract：:Daily rhythms in behavior, physiology, and metabolism are an integral part of homeostasis. These rhythms emerge from interactions between endogenous circadian clocks and ambient light-dark cycles, sleep-activity cycles, and eating-fasting cycles. Nearly the entire primate genome shows daily rhythms in expression in ti...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.07.003
更新日期：2018-09-01 00:00:00
abstract：:All currently available general anesthetics produce potentially deadly side effects. Unfortunately, few approaches have been developed to design safer ones, despite important advances in anesthetic mechanisms research. Cayla and colleagues recently showed that computational methods can be used to identify anesthetic l...
journal_title：Trends in pharmacological sciences
pub_type： 评论,杂志文章
doi：10.1016/j.tips.2019.09.001
更新日期：2019-11-01 00:00:00
abstract：:Gene therapy is a new field of medical research that has great potential to influence the course of treatment of human disease. The lung has been a particularly attractive target organ for gene therapy due to its accessibility and the identification of genetic deficits for a number of lung diseases. Several clinical t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01350-4
更新日期：1999-06-01 00:00:00
abstract：:Regulators of G-protein signaling (RGS proteins) comprise a large family of signal transduction molecules that modulate G-protein-coupled-receptor (GPCR) function. Among the RGS proteins expressed in the brain, RGS9-2 is very abundant in the striatum, a brain region involved in movement, motivation, mood and addiction...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2008.11.006
更新日期：2009-03-01 00:00:00
abstract：:The translocator protein (TSPO), an 18-kDa transmembrane protein primarily found in the outer mitochondrial membrane, is evolutionarily conserved and widely distributed across species. In mammals, TSPO has been described as a key member of a multiprotein complex involved in many putative functions and, over the years,...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.11.005
更新日期：2020-02-01 00:00:00
abstract：:Carbonic anhydrase isoform IX (CA IX) is highly overexpressed in many types of cancer. Its expression, which is regulated by the HIF-1 transcription factor, is strongly induced by hypoxia and correlates with a poor response to classical chemo- and radiotherapies. CA IX contributes to acidification of the tumor environ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2006.09.002
更新日期：2006-11-01 00:00:00
abstract：:An unlikely animal model is gaining popularity in neuropharmacological research: the 2-mm fruit fly (Drosophila melanogaster). Drugs have been administered to adult flies in their food and, more recently, via gasses and injections. Pharmacological tools have introduced behavioral alterations in Drosophila reminiscent ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(02)00004-4
更新日期：2003-01-01 00:00:00
