Abstract：
:The characterization of P2 gamma purinoceptors on vascular endothelial cells has progressed rapidly since their existence was first demonstrated in 1983. They transduce the actions of extracellular ATP and ADP--endothelium-dependent relaxation, prostacyclin synthesis, endothelial cell mitogenesis--which play a vital role in the interaction between platelets (a rich source of extracellular adenine nucleotides) and the vessel wall. Release of prostacyclin limits the extent of intravascular platelet aggregation following vascular damage and platelet stimulation, while the mitogenic effect may accelerate the repair of a lesion. P2 gamma receptors on endothelial cells are coupled to a phospholipase C by a GTP-binding protein. Jean-Marie Boeynaems and Jeremy Pearson explain how the increases in cytoplasmic Ca2+ and diacylglycerol resulting from this initial event mediate several further effects. In particular, activation of a Ca2(+)-sensitive phospholipase A2 explains the increased synthesis of prostacyclin, while the phosphorylation of several proteins by calmodulin-dependent kinases modulates other endothelial cell functions.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Boeynaems JM,Pearson JDdoi
10.1016/0165-6147(90)90039-bsubject
Has Abstractpub_date
1990-01-01 00:00:00pages
34-7issue
1eissn
0165-6147issn
1873-3735pii
0165-6147(90)90039-Bjournal_volume
11pub_type
杂志文章,评审abstract：:Addiction biology has focused on the mechanisms of the positive and negative reinforcing actions of addictive drugs but neglected potential benefits. Two new studies provide the first insights into a neurobiology of psychoactive drug instrumentalization. This may help us design better models for addiction neuroscience...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2017.03.005
更新日期：2017-06-01 00:00:00
abstract：:It has taken 17 years from the first identification of a voltage-gated Ca2+ channel (CaV) beta-subunit as a band on a gel following purification of skeletal muscle dihydropyridine (DHP) receptors in 1987 to the publication of key information on the structures of Ca2+ channel beta-subunits. Three recent X-ray crystallo...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2004.10.008
更新日期：2004-12-01 00:00:00
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
pub_type： 杂志文章,评审
doi：
更新日期：1996-10-01 00:00:00
abstract：:Oxidative stress is a key pathologic factor in neurodegenerative diseases such as Alzheimer and Parkinson diseases (AD, PD). The failure of free-radical-scavenging antioxidants in clinical trials pinpoints an urgent need to identify and to block major sources of oxidative stress in neurodegenerative diseases. As a maj...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2012.03.008
更新日期：2012-06-01 00:00:00
abstract：:Inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease (PR) are widely used in the clinical treatment of AIDS. However, the emergence of drug-resistant variants of HIV-1 severely limits the long-term effectiveness of these drugs. In this review, the molecular basis of resista...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(02)02054-0
更新日期：2002-08-01 00:00:00
abstract：:Cardiovascular disease remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves epoxyeicosatrienoic acid (EET) and soluble epoxide hydroxylase (sEH) inhibition. sEH is the enzyme that converts EET to its less potent metabolite; therefore...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.08.001
更新日期：2016-11-01 00:00:00
abstract：:Traditional African medicine (TAM) is a shorthand reference to indigenous forms of healing that are practiced all over Africa. Although TAM is based on the accumulated experience of ancient Africans, its mode of transmission by word-of-mouth has hindered emergence of a generally accepted theory and hence of the system...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01406-6
更新日期：1999-12-01 00:00:00
abstract：:Fatty acid amide hydrolase (FAAH) is a hydrolytic enzyme that recognizes as substrates and inactivates the two most studied endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG). Following the observation that endocannabinoids produced by tissues during pathological conditions often have protective roles, FAA...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2008.03.001
更新日期：2008-05-01 00:00:00
abstract：:Endothelial-dependent relaxation of vascular smooth muscle cells evoked by a number of agonists, including cholinomimetics and substance P, is often accompanied by an increase (repolarization and/or hyperpolarization) in the membrane potential. This change in membrane potential appears predominantly to reflect the act...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)88969-5
更新日期：1995-01-01 00:00:00
abstract：:Nearly all molecules known to signal cells via G proteins have been assigned a cloned G-protein-coupled-receptor (GPCR) gene. This has been the result of a decade-long genetic search that has also identified some receptors for which ligands are unknown; these receptors are described as orphans (oGPCRs). More than 80 o...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01366-8
更新日期：1999-09-01 00:00:00
abstract：:Dimerization is fairly common in the G-protein-coupled receptor (GPCR) superfamily. First attempts to rationalize this phenomenon gave rise to an idea that two receptors in a dimer could be necessary to bind a single molecule of G protein or arrestin. Although GPCRs, G proteins and arrestins were crystallized only in ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2008.02.004
更新日期：2008-05-01 00:00:00
abstract：:Changes in the structure and function of the small airways (<2mm diameter) are now recognized to play a major role in airflow limitation in both chronic obstructive pulmonary disease (COPD) and severe asthma. Increased thickness of the small airway wall causes lumenal narrowing, which can be further occluded by mucus ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2008.04.003
更新日期：2008-07-01 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：:In the conventional view, GABA acts at either ionotropic GABAA or metabotropic GABAB receptors. Recently, novel ionotropic GABA receptors that are composed of rho-subunits have been identified in the vertebrate retina. These bicuculline- and baclofen-insensitive GABA receptors are frequently called GABAC, following an...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01413-3
更新日期：2000-01-01 00:00:00
abstract：:The sialic-acid-binding immunoglobulin-like lectins (siglecs) comprise a family of receptors that are differentially expressed on leukocytes and other immune cells. The restricted expression of several siglecs to one or a few cell types makes them attractive targets for cell-directed therapies. The anti-CD33 (also kno...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2009.02.005
更新日期：2009-05-01 00:00:00
abstract：:Cannabis (marijuana) is not only a frequently abused drug but also has the potential for the development of useful agents for the treatment of emesis, anorexia and multiple sclerosis. In this article, the effects of modulation of transmitter release by cannabinoids in both the CNS and the PNS of various species, inclu...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01805-8
更新日期：2001-11-01 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：:Since G protein-coupled receptors (GPCRs) belong to a very large superfamily of evolutionarily related receptors (>800 members in humans), and due to the rapid progress on their structural biology, they are ideal candidates for polypharmacology studies. Broad screening and bioinformatics/chemoinformatics have been app...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2014.10.009
更新日期：2014-12-01 00:00:00
abstract：:The vascular endothelium is a remarkably heterogeneous organ. In addition to well-characterized anatomical diversity in situ, specific differences are increasingly being recognized between surface antigens on endothelial cells from different tissues, including absence of the classic endothelial marker factor VIII-rela...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(91)90637-8
更新日期：1991-12-01 00:00:00
abstract：:Hormesis is a generalizable dose-response relationship characterized by low-dose stimulation and high-dose inhibition. Despite debate over this biphasic dose-response curve, hormesis is challenging central beliefs in the evaluation of chemicals or drugs and has influenced biological model selection, concentration rang...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2020.05.004
更新日期：2020-08-01 00:00:00
abstract：:For almost 70 years, children have received stimulants for the treatment of attention deficit hyperactivity disorder [ADHD (initially called hyperkinetic syndrome)], with little understanding of the long-term effects of these drugs on brain development. The maturation and refinement of the brain during childhood and a...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.03.009
更新日期：2005-05-01 00:00:00
abstract：:It is now established that most of the approximately 800 G-protein-coupled receptors (GPCRs) are regulated by phosphorylation in a process that results in the recruitment of arrestins, leading to receptor desensitization and the activation of arrestin-dependent processes. This generalized view of GPCR regulation, howe...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2008.05.006
更新日期：2008-08-01 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
pub_type： 杂志文章
doi：10.1016/j.tips.2007.03.003
更新日期：2007-05-01 00:00:00
abstract：:Lithium is the simplest therapeutic agent available for the treatment of depression and has been used for over 100 years, yet no definitive mechanism for its effect has been established. Among the proposed mechanisms, two lithium-sensitive signal transduction pathways are active in the brain; these are mediated by gly...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/s0165-6147(99)01428-5
更新日期：2000-02-01 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：: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
pub_type： 评论,杂志文章
doi：10.1016/j.tips.2018.06.005
更新日期：2018-09-01 00:00:00
abstract：:Cytochromes P450 are a superfamily of haem-containing monooxygenases. In mammals, two general classes of P450s exist: six families involved in steroid and bile acid biosynthetic pathways of metabolism; four families containing numerous individual P450s, mainly responsible for metabolism of foreign compounds. Many of t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(92)90107-h
更新日期：1992-09-01 00:00:00
abstract：:There is increasing awareness of the compartmentalization of cAMP signalling--the means by which cAMP levels change in discrete domains of the cell with discrete local consequences. Current developments in understanding the organization of adenylyl cyclases in the plasma membrane are illuminating how the earliest part...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.06.002
更新日期：2006-08-01 00:00:00
abstract：:Snake venom neurotoxins and lymphocyte antigen 6 (Ly6) proteins, most of the latter being membrane tethered by a glycosylphosphatidylinositol (GPI) anchor, have a variety of biological activities, but their three-finger (3F) folding combines them in one Ly6/neurotoxin family. Subsets of two groups, represented by α-ne...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.11.003
更新日期：2015-02-01 00:00:00
abstract：:The purpose of this Opinion is to present a case for targeting sphingosine kinase 2 (SK2) in autoimmune/inflammatory disease. Data obtained using Sphk2-/- mice suggest that SK2 is an anti-inflammatory enzyme, although this might be misleading because of a compensatory increase in the expression of a second isoform, sp...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2017.04.003
更新日期：2017-07-01 00:00:00
