Muscarinic activation of potassium channels in cardiac myocytes: kinetic aspects of G protein function in vivo.

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

authors： John P,Wei Y,Liu W,Du M,Guan F,Zang X

更新日期：2019-11-01 00:00:00

abstract：:Parkinson's disease (PD) is a progressive neurodegenerative disorder. Although therapies that treat the symptoms of the disease have proven efficacy, strategies that slow or stop the neurodegenerative process are currently not available. Recently, the National Institute of Neurological Disorders and Stroke (NINDS) con...

journal_title：Trends in pharmacological sciences

authors： Meissner W,Hill MP,Tison F,Gross CE,Bezard E

更新日期：2004-05-01 00:00:00

abstract：:Due to its negative chronotropic and inotropic effects, adenosine has to date been considered as a cardiodepressant agent. However, adenosine increases ventricular automaticity. This review by Jesus Hernández and Alexandre Ribeiro discusses the experimental and clinical evidence for the excitatory effects of adenosine...

journal_title：Trends in pharmacological sciences

authors： Hernández J,Ribeiro JA

更新日期：1996-04-01 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：:Adenosine, when given by inhalation, initiates the narrowing of airways in subjects with asthma or chronic obstructive pulmonary disease (COPD). The underlying mechanism of this narrowing appears to involve the stimulation of specific mast cell surface adenosine receptors with the subsequent release of mediators and c...

journal_title：Trends in pharmacological sciences

authors： Spicuzza L,Bonfiglio C,Polosa R

更新日期：2003-08-01 00:00:00

abstract：:Efforts to model and reengineer the putative binding sites of G-protein-coupled receptors (GPCRs) have led to an approach that combines small-molecule 'classical' medicinal chemistry and gene therapy. In this approach, complementary structural changes (e.g. based on novel ionic or H-bonds) are made in the receptor and...

journal_title：Trends in pharmacological sciences

authors： Jacobson KA,Gao ZG,Liang BT

更新日期：2007-03-01 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

authors： Moriyama Y,Nomura M

更新日期：2018-01-01 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

authors： Williams RS,Harwood AJ

更新日期：2000-02-01 00:00:00

abstract：:During the past decade remarkable progress in molecular genetics and the possibility of manipulating cells so that the expression of genes can directly 'report' on drug activity has produced major changes in drug development strategies. The recent description and pharmacological validation of reporter mice for in vivo...

journal_title：Trends in pharmacological sciences

authors： Maggi A,Ottobrini L,Biserni A,Lucignani G,Ciana P

更新日期：2004-06-01 00:00:00

abstract：:Recruitment of leukocytes either during development or to the site of injury is crucial. The molecular regulation of cell trafficking is complex but well orchestrated by the temporal and spatial expression of a multitude of chemokines (chemoattractant cytokines) and chemokine receptors. The chemokines, classified prim...

journal_title：Trends in pharmacological sciences

authors： Devalaraja MN,Richmond A

更新日期：1999-04-01 00:00:00

abstract：:Genes encoding glutamate receptor channel subunits were identified in genomes from Drosophila melanogaster and Caenorhabditis elegans by homology search with amino acid sequences that participate in the conserved channel pore. The predicted sequences of the putative glutamate receptor subunits revealed a distinct chan...

journal_title：Trends in pharmacological sciences

authors： Sprengel R,Aronoff R,Völkner M,Schmitt B,Mosbach R,Kuner T

更新日期：2001-01-01 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

authors： Manev H,Dimitrijevic N,Dzitoyeva S

更新日期：2003-01-01 00:00:00

abstract：:Over the past few decades, mortality resulting from cardiovascular disease (CVD) steadily decreased in western countries; however, in recent years, the decline has become offset by the increase in obesity. Obesity is strongly associated with the metabolic syndrome and its atherogenic dyslipidemia resulting from insuli...

journal_title：Trends in pharmacological sciences

authors： Soyal SM,Nofziger C,Dossena S,Paulmichl M,Patsch W

更新日期：2015-06-01 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

authors： Pyne NJ,Adams DR,Pyne S

更新日期：2017-07-01 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：:It has been suggested that G protein-coupled receptors can act as proton transporters, with the activated G protein-coupled receptor transporting H+ across the membrane from the extracellular side to the cytoplasm. In this article, Paul Nederkoorn, Henk Timmerman and Gabriëlle Donné-Op den Kelder summarize the various...

journal_title：Trends in pharmacological sciences

authors： Nederkoorn PH,Timmerman H,Donné-Op den Kelder GM

更新日期：1995-05-01 00:00:00

abstract：:Apoptosis plays a key role in tumour biology, and the induction of apoptosis forms a cornerstone of most anticancer therapies. New developments in nuclear magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) have taken these techniques far beyond their original roles as the workhorses of structur...

journal_title：Trends in pharmacological sciences

authors： Hakumäki JM,Brindle KM

更新日期：2003-03-01 00:00:00

abstract：:Pathogenic granulocytes (eosinophils and neutrophils) infiltrate airway tissues in asthma and chronic obstructive pulmonary disease. Granulocytes release tissue-toxic and inflammatory mediators, making their removal an important pharmacological goal. Removal is thought to be accomplished through apoptosis followed by ...

journal_title：Trends in pharmacological sciences

authors： Uller L,Persson CG,Erjefält JS

更新日期：2006-09-01 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

authors： Dinarello CA

更新日期：1993-05-01 00:00:00

abstract：:Platelet activating factor (PAF) is a phospholipid mediator of inflammation and stimulates anion secretion in animals and in isolated preparations of human colon. Nitric oxide (NO), synthesized from the amino acid L-arginine, is an important enteric inhibitory neurotransmitter. In addition, NO-donating compounds stimu...

journal_title：Trends in pharmacological sciences

authors： Izzo AA,Gaginella TS,Mascolo N,Capasso F

更新日期：1998-10-01 00:00:00

abstract：:Delayed biochemical changes play an important role in tissue damage resulting from traumatic injuries to the central nervous system. Identification of such 'secondary' injury factors has led to the development of various pharmacological strategies aimed at limiting this progressive tissue destruction. In this review, ...

journal_title：Trends in pharmacological sciences

authors： Faden AI,Salzman S

更新日期：1992-01-01 00:00:00

abstract：:Mitogen-activated protein kinases [MAPKs, also called extracellular signal-regulated kinases (ERKs)] are constituents of numerous signal transduction pathways, and are activated by protein kinase cascades. Intense efforts are under way to develop and evaluate compounds that target components of MAPK pathways. In this ...

journal_title：Trends in pharmacological sciences

authors： English JM,Cobb MH

更新日期：2002-01-01 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

authors： Malumbres M,Pevarello P,Barbacid M,Bischoff JR

更新日期：2008-01-01 00:00:00

abstract：:This year marks the 90th anniversary of the publication of Hans Horst Meyer's classic paper in which he proposed that the ability of a substance to produce narcosis or anesthesia is governed by its partition coefficient. In this article, Robert Lipnick describes the experiments carried out by Meyer and his colleagues ...

journal_title：Trends in pharmacological sciences

authors： Lipnick RL

更新日期：1989-07-01 00:00:00

abstract：:Recent studies have proposed a functional link between annexin 1 (ANXA1), an endogenous anti-inflammatory mediator, and receptors of the formyl-peptide family. In particular, exogenous and endogenous ANXA1 and its peptidomimetics interact with one member of this family, the formyl-peptide-receptor-like 1. Further anal...

journal_title：Trends in pharmacological sciences

authors： Perretti M

更新日期：2003-11-01 00:00:00

abstract：:The concept that receptors can exist in multiple conformational states is becoming a physical reality. A fundamental question is how many active states need to be proposed in order to account for pharmacological observations, in particular, the finding that the same receptor type can exhibit a different agonist pharma...

journal_title：Trends in pharmacological sciences

authors： Leff P,Scaramellini C,Law C,McKechnie K

更新日期：1997-10-01 00:00:00

abstract：:Although an established regulator of many cellular functions, the phosphoinositide phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2) appears to have evaded the attention of drug-discovery companies. An increasing number of reports have identified potential links between PtdIns(4,5)P2-mediated signalling pathways...

journal_title：Trends in pharmacological sciences

authors： Halstead JR,Jalink K,Divecha N

更新日期：2005-12-01 00:00:00

abstract：:Neuronal Ca2+-sensor (NCS) proteins constitute a subfamily of closely related EF-hand Ca2+-binding proteins that are expressed mainly in neurons or retinal photoreceptor cells. A variety of different neuronal functions have been attributed to these proteins. However, important new discoveries indicate that these prote...

journal_title：Trends in pharmacological sciences

authors： Braunewell KH

更新日期：2005-07-01 00:00:00

abstract：:14-3-3 Proteins enact a range of cellular functions through protein-protein interactions (PPIs) with client proteins. Kaplan and colleagues recently demonstrated that a semisynthetic compound was able to selectively stabilize or disrupt specific interactions, depending on the binding partner. This finding presents an ...

journal_title：Trends in pharmacological sciences

authors： Gannon M,Yacoubian TA

更新日期：2020-07-01 00:00:00

abstract：:Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easil...

journal_title：Trends in pharmacological sciences

authors： Coskun M,Vermeire S,Nielsen OH

更新日期：2017-02-01 00:00:00