Novel interactions between K+ channels and scorpion toxins.

Abstract:

:K(+) channels are macromolecules embedded in biological membranes, where they play a key role in cellular excitability and signal transduction pathways. Knowledge of their structure should help improve our understanding of their function and lead to the design of therapeutic compounds. Most pharmacological and structural characteristics of these channels have been elucidated by using high-affinity channel blockers isolated from scorpion venoms. Recent data on the three-dimensional structures of K(+) channels and novel scorpion toxins suggest a variety of novel interacting modes of these channels and toxins, which should help increase our understanding of the K(+) channel structure-function relationship.

journal_name

Trends Pharmacol Sci

authors

Rodríguez de la Vega RC,Merino E,Becerril B,Possani LD

doi

10.1016/S0165-6147(03)00080-4

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

222-7

issue

5

eissn

0165-6147

issn

1873-3735

pii

S0165-6147(03)00080-4

journal_volume

24

pub_type

杂志文章,评审
  • Molecular enzymology of human liver cytosolic sulfotransferases.

    abstract::Sulfoconjugation of drugs and small xenobiotic and endogenous compounds in human tissues is primarily catalysed by cytosolic forms of sulfotransferase. In most instances, sulfate conjugation is associated with a decrease in the biological activity and an increase in the excretion of the sulfated compounds. However, su...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(91)90566-b

    authors: Falany CN

    更新日期:1991-07-01 00:00:00

  • Toxicology of simple and complex mixtures.

    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

    authors: Groten JP,Feron VJ,Sühnel J

    更新日期:2001-06-01 00:00:00

  • Cancer and Microenvironment Plasticity: Double-Edged Swords in Metastasis.

    abstract::Cancer initiates at one site (primary tumor) and, in most cases, spreads to other distant organs (metastasis). During the multistep process of metastasis, primary tumor cells acquire cellular and phenotypic plasticity to survive and thrive in different environments. Moreover, cancer cells also utilize and educate micr...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2019.04.005

    authors: Zhuang X,Zhang H,Hu G

    更新日期:2019-06-01 00:00:00

  • How and why do GPCRs dimerize?

    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

    authors: Gurevich VV,Gurevich EV

    更新日期:2008-05-01 00:00:00

  • Beyond vasodilatation: non-vasomotor roles of epoxyeicosatrienoic acids in the cardiovascular system.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2006.11.002

    authors: Larsen BT,Campbell WB,Gutterman DD

    更新日期:2007-01-01 00:00:00

  • Computational studies to predict or explain G protein coupled receptor polypharmacology.

    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

    authors: Jacobson KA,Costanzi S,Paoletta S

    更新日期:2014-12-01 00:00:00

  • Are formyl peptide receptors novel targets for therapeutic intervention in ischaemia-reperfusion injury?

    abstract::Ischaemia-reperfusion (I/R) injury is a common feature of several diseases associated with high morbidity and mortality, such as stroke and myocardial infarction. The damaged tissue displays cardinal signs of inflammation and microvascular injury that, unless resolved, lead to long-term tissue damage with associated d...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2010.04.001

    authors: Gavins FN

    更新日期:2010-06-01 00:00:00

  • Assay strategies for identification of therapeutic leads that target protein trafficking.

    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

    authors: Conn PM,Spicer TP,Scampavia L,Janovick JA

    更新日期:2015-08-01 00:00:00

  • Preclinical models of antipsychotic drug-induced metabolic side effects.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2010.07.002

    authors: Boyda HN,Tse L,Procyshyn RM,Honer WG,Barr AM

    更新日期:2010-10-01 00:00:00

  • Nicotine addiction: the possible role of functional upregulation.

    abstract::Upregulation of binding to nicotinic acetylcholine receptors (nAChRs) is observed in the brains of both smokers and animals chronically exposed to nicotine, although whether this in vivo change is accompanied by an increase in receptor function is unknown. In vitro recordings indicate that alpha4beta2- and alpha7-subt...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/S0165-6147(00)01979-9

    authors: Buisson B,Bertrand D

    更新日期:2002-03-01 00:00:00

  • P2 purinoceptors on vascular endothelial cells: physiological significance and transduction mechanisms.

    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 r...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(90)90039-b

    authors: Boeynaems JM,Pearson JD

    更新日期:1990-01-01 00:00:00

  • Peptidomics for the discovery and characterization of neuropeptides and hormones.

    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 trem...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2015.05.009

    authors: Romanova EV,Sweedler JV

    更新日期:2015-09-01 00:00:00

  • Regulation of transcription factor activity by interconnected post-translational modifications.

    abstract::Transcription factors comprise just over 7% of the human proteome and serve as gatekeepers of cellular function, integrating external signal information into gene expression programs that reconfigure cellular physiology at the most basic levels. Surface-initiated cell signaling pathways converge on transcription facto...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2013.11.005

    authors: Filtz TM,Vogel WK,Leid M

    更新日期:2014-02-01 00:00:00

  • Machine Learning for Biologics: Opportunities for Protein Engineering, Developability, and Formulation.

    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

    authors: Narayanan H,Dingfelder F,Butté A,Lorenzen N,Sokolov M,Arosio P

    更新日期:2021-01-23 00:00:00

  • Ischaemic preconditioning of the vasculature: an overlooked phenomenon for protecting the heart?

    abstract::Exposing the heart to brief episodes of ischaemia protects the myocardium and vascular endothelial cells against functional damage and cell death caused by subsequent prolonged ischaemia. Elucidation of the mechanisms that are involved in this phenomenon known as 'ischaemic preconditioning' and identification of drugs...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(00)01483-8

    authors: Rubino A,Yellon DM

    更新日期:2000-06-01 00:00:00

  • A brief history of British Pharmacological Society meetings.

    abstract::The British Pharmacological Society (BPS) is currently celebrating its 75th anniversary. It is therefore a young society compared with some other biomedical societies and particularly when compared with the origins of the oldest learned societies. In this article, I briefly review the origins of learned societies and ...

    journal_title:Trends in pharmacological sciences

    pub_type: 历史文章,杂志文章

    doi:10.1016/j.tips.2006.01.001

    authors: Green AR

    更新日期:2006-03-01 00:00:00

  • Toward understanding ubiquitin-modifying enzymes: from pharmacological targeting to proteomics.

    abstract::Ubiquitination is a highly conserved post-translational modification that regulates protein trafficking, function, and turnover. Ubiquitin ligases (E3s) conjugate ubiquitin polypeptides on substrates, whereas deubiquitnases (DUBs) reverse ubiquitination. Engineering of chemical antagonists and inhibitors of ubiquitin ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2014.01.005

    authors: Lill JR,Wertz IE

    更新日期:2014-04-01 00:00:00

  • Targeting HIV: antiretroviral therapy and development of drug resistance.

    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

    authors: Menéndez-Arias L

    更新日期:2002-08-01 00:00:00

  • Erythropoietin in the brain: can the promise to protect be fulfilled?

    abstract::Erythropoietin (EPO) has emerged as a versatile growth factor that has transcended its traditional role as a mediator of erythroid maturation to one that modulates stem cell development, cellular protection and angiogenesis in the brain. As a possible candidate for nervous system disorders, it becomes crucial to under...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2004.09.006

    authors: Maiese K,Li F,Chong ZZ

    更新日期:2004-11-01 00:00:00

  • Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria.

    abstract::Drugs that cause liver injury often 'stress' mitochondria and activate signal transduction pathways important in determining cell survival or death. In most cases, hepatocytes adapt to the drug-induced stress by activating adaptive signaling pathways, such as mitochondrial adaptive responses and nuclear factor erythro...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2013.01.009

    authors: Han D,Dara L,Win S,Than TA,Yuan L,Abbasi SQ,Liu ZX,Kaplowitz N

    更新日期:2013-04-01 00:00:00

  • Thiol-Based Drugs in Pulmonary Medicine: Much More than Mucolytics.

    abstract::Thiol-based drugs are considered as mucolytics because they decrease the viscosity and mostly decrease the elasticity of bronchial secretions by reducing disulfide bonds in proteins. However, they can also act as antioxidant drugs directly through free sulfhydryl groups that serve as a source of reducing equivalents, ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.tips.2019.04.015

    authors: Cazzola M,Calzetta L,Page C,Rogliani P,Matera MG

    更新日期:2019-07-01 00:00:00

  • Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.

    abstract::Hypercontraction or abnormal contraction of vascular smooth muscle is a major cause of diseases such as hypertension and vasospasm of the coronary and cerebral arteries. A better understanding of the mechanism of regulation of smooth muscle contraction should lead to improved treatments for such diseases. Recent studi...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(00)01596-0

    authors: Fukata Y,Amano M,Kaibuchi K

    更新日期:2001-01-01 00:00:00

  • Precision Medicine through Antisense Oligonucleotide-Mediated Exon Skipping.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2018.09.001

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

    更新日期:2018-11-01 00:00:00

  • Higher-order organization and regulation of adenylyl cyclases.

    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

    authors: Cooper DM,Crossthwaite AJ

    更新日期:2006-08-01 00:00:00

  • 007 (x2)-3-3: 14-3-3 Targeted Compounds as Double Agents.

    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

    pub_type: 评论,杂志文章

    doi:10.1016/j.tips.2020.05.001

    authors: Gannon M,Yacoubian TA

    更新日期:2020-07-01 00:00:00

  • NAADP: an atypical Ca2+-release messenger?

    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

    authors: Genazzani AA,Billington RA

    更新日期:2002-04-01 00:00:00

  • The annexin 1 receptor(s): is the plot unravelling?

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2003.09.010

    authors: Perretti M

    更新日期:2003-11-01 00:00:00

  • Size matters in activation/inhibition of ligand-gated ion channels.

    abstract::Cys loop, glutamate, and P2X receptors are ligand-gated ion channels (LGICs) with 5, 4, and 3 protomers, respectively. There is now growing atomic level understanding of their gating mechanisms. Although each family is unique in the architecture of the ligand-binding pocket, the pathway for motions to propagate from l...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2012.06.005

    authors: Du J,Dong H,Zhou HX

    更新日期:2012-09-01 00:00:00

  • Diverse functions of muscarinic acetylcholine receptor subtypes.

    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:

    authors: Lechleiter J,Peralta E,Clapham D

    更新日期:1989-12-01 00:00:00

  • Agonist regulation of cellular G protein levels and distribution: mechanisms and functional implications.

    abstract::Exposure of cells to agonists of receptors linked to G proteins can result in downregulation of cellular levels or redistribution of G proteins from membranes to the cytosol. Agonist-induced reductions in G protein levels have been observed for members of each of the Gs, Gi and Gq families of G proteins, are likely to...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(93)90064-Q

    authors: Milligan G

    更新日期:1993-11-01 00:00:00