Caveolae as organizers of pharmacologically relevant signal transduction molecules.

Abstract:

:Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations of the plasma membrane that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N and C termini, palmitolylation sites, and a scaffolding domain that facilitates interaction and organization of signaling molecules so as to help provide coordinated and efficient signal transduction. Such signaling components include upstream entities (e.g., G protein-coupled receptors (GPCRs), receptor tyrosine kinases, and steroid hormone receptors) and downstream components (e.g., heterotrimeric and low-molecular-weight G proteins, effector enzymes, and ion channels). Diseases associated with aberrant signaling may result in altered localization or expression of signaling proteins in caveolae. Caveolin-knockout mice have numerous abnormalities, some of which may reflect the impact of total body knockout throughout the life span. This review provides a general overview of caveolins and caveolae, signaling molecules that localize to caveolae, the role of caveolae/caveolin in cardiac and pulmonary pathophysiology, pharmacologic implications of caveolar localization of signaling molecules, and the possibility that caveolae might serve as a therapeutic target.

authors

Patel HH,Murray F,Insel PA

doi

10.1146/annurev.pharmtox.48.121506.124841

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

359-91

eissn

0362-1642

issn

1545-4304

journal_volume

48

pub_type

杂志文章,评审
  • Pharmacological implications of the flow-dependence of vascular smooth muscle tone.

    abstract::The recognition that the wall tone of most arteries and veins can change in response to shear stress has several implications for our understanding of the effects of drugs on the circulation. By a primary action on the heart and vasculature, drugs can cause changes in cardiac output and blood pressure that lead to cha...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pa.34.040194.001133

    authors: Bevan JA,Henrion D

    更新日期:1994-01-01 00:00:00

  • Oral Biologic Delivery: Advances Toward Oral Subunit, DNA, and mRNA Vaccines and the Potential for Mass Vaccination During Pandemics.

    abstract::Oral vaccination enables pain-free and self-administrable vaccine delivery for rapid mass vaccination during pandemic outbreaks. Furthermore, it elicits systemic and mucosal immune responses. This protects against infection at mucosal surfaces, which may further enhance protection and minimize the spread of disease. T...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章

    doi:10.1146/annurev-pharmtox-030320-092348

    authors: Coffey JW,Gaiha GD,Traverso G

    更新日期:2021-01-06 00:00:00

  • Organophosphorus Xenobiotic Toxicology.

    abstract::Originally, organophosphorus (OP) toxicology consisted of acetylcholinesterase inhibition by insecticides and chemical threat agents acting as phosphorylating agents for serine in the catalytic triad, but this is no longer the case. Other serine hydrolases can be secondary OP targets, depending on the OP structure, an...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-010716-104926

    authors: Casida JE

    更新日期:2017-01-06 00:00:00

  • Developmental neuropathology of environmental agents.

    abstract::The developing central nervous system (CNS) is more vulnerable to injury than the adult one. Although a great deal of research has been devoted to subtle effects of developmental exposure, such as neurobehavioral changes, this review instead focuses on a number of chemicals that have been shown, in several experimenta...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.44.101802.121424

    authors: Costa LG,Aschner M,Vitalone A,Syversen T,Soldin OP

    更新日期:2004-01-01 00:00:00

  • Chronopharmacology: new insights and therapeutic implications.

    abstract::Most facets of mammalian physiology and behavior vary according to time of day, thanks to endogenous circadian clocks. Therefore, it is not surprising that many aspects of pharmacology and toxicology also oscillate according to the same 24-h clocks. Daily oscillations in abundance of proteins necessary for either drug...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-011613-135923

    authors: Dallmann R,Brown SA,Gachon F

    更新日期:2014-01-01 00:00:00

  • Hepatic and intestinal drug transporters: prediction of pharmacokinetic effects caused by drug-drug interactions and genetic polymorphisms.

    abstract::Recent studies of membrane transporters have revealed their importance in determining the pharmacokinetics of transporter substrates. When drug-drug interactions (DDIs) or genetic polymorphisms (i.e., pharmacogenetics) affect the activities of transporters, the pharmacokinetics of transporter substrate drugs is altere...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-011112-140309

    authors: Yoshida K,Maeda K,Sugiyama Y

    更新日期:2013-01-01 00:00:00

  • The ethics and economics of pharmaceutical pricing.

    abstract::The cost of drugs is a major and rapidly rising component of health-care expenditures. We survey recent literature on the ethics and economics of skyrocketing pharmaceutical prices and find that advances in economic research have increased the sharpness and focus of the ethically based calls to increase access by modi...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-010814-124649

    authors: Parker-Lue S,Santoro M,Koski G

    更新日期:2015-01-01 00:00:00

  • Drugs for allosteric sites on receptors.

    abstract::The presence of druggable, topographically distinct allosteric sites on a wide range of receptor families has offered new paradigms for small molecules to modulate receptor function. Moreover, ligands that target allosteric sites offer significant advantages over the corresponding orthosteric ligands in terms of selec...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-010611-134525

    authors: Wenthur CJ,Gentry PR,Mathews TP,Lindsley CW

    更新日期:2014-01-01 00:00:00

  • Neurokinin(1) receptor antagonists as potential antidepressants.

    abstract::Selective, nonpeptide antagonists for tachykinin receptors first became available ten years ago. Of the three known tachykinin receptors, drug development has focused most intensively on the substance P-preferring receptor, neurokinin(1) (NK(1)). Although originally studied as potential analgesic compounds, recent evi...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.41.1.877

    authors: Stout SC,Owens MJ,Nemeroff CB

    更新日期:2001-01-01 00:00:00

  • Signaling networks in living cells.

    abstract::Recent advances in cell signaling research suggest that multiple sets of signal transducing molecules are preorganized and sequestered in distinct compartments within the cell. These compartments are assembled and maintained by specific cellular machinery. The molecular ecology within a compartment creates an environm...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.45.120403.095807

    authors: White MA,Anderson RG

    更新日期:2005-01-01 00:00:00

  • Learning by failing: ideas and concepts to tackle γ-secretases in Alzheimer's disease and beyond.

    abstract::γ-Secretases are a group of widely expressed, intramembrane-cleaving proteases involved in many physiological processes. Their clinical relevance comes from their involvement in Alzheimer's disease, cancer, and other disorders. A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, de...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-010814-124309

    authors: De Strooper B,Chávez Gutiérrez L

    更新日期:2015-01-01 00:00:00

  • Human Induced Pluripotent Stem Cell (hiPSC)-Derived Cells to Assess Drug Cardiotoxicity: Opportunities and Problems.

    abstract::Billions of US dollars are invested every year by the pharmaceutical industry in drug development, with the aim of introducing new drugs that are effective and have minimal side effects. Thirty percent of in-pipeline drugs are excluded in an early phase of preclinical and clinical screening owing to cardiovascular saf...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-010617-053110

    authors: Magdy T,Schuldt AJT,Wu JC,Bernstein D,Burridge PW

    更新日期:2018-01-06 00:00:00

  • Tumor cell death induced by topoisomerase-targeting drugs.

    abstract::DNA topoisomerases are double-edged swords. They are essential for many vital functions of DNA during normal cell growth. However, they are also highly vulnerable under various physiological and nonphysiological stresses because of their delicate act on breaking and rejoining DNA. These stresses (e.g. exposure to topo...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.41.1.53

    authors: Li TK,Liu LF

    更新日期:2001-01-01 00:00:00

  • Metallothioneins and cell death by anticancer drugs.

    abstract::Both pharmacologic and genetic methods are now available to manipulate intracellular levels of the protein thiol metallothionein. These approaches have begun to reveal the protective roles metallothioneins (MTs) have against oxygen, nitrogen, and carbon-centered free radicals, as well as the contributory role of MT to...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pa.35.040195.003223

    authors: Lazo JS,Pitt BR

    更新日期:1995-01-01 00:00:00

  • A personal view of pharmacology.

    abstract::This essay is an account of the author's experience in trying to interpret the action of drugs as seen in in vitro bioassays. The central theme is how the development of simple mathematical models has assisted in the interpretation of drug actions. Starting from encounters with partial agonists, the essay describes th...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 传,历史文章,杂志文章,评审

    doi:10.1146/annurev.pa.36.040196.000245

    authors: Black J

    更新日期:1996-01-01 00:00:00

  • The potential of farnesyltransferase inhibitors as cancer chemotherapeutics.

    abstract::Mutant ras oncogenes and alterations in the mitogenic signaling pathways that they regulate are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. Of the possible approaches to inhibit Ras function, much attention has focused on a posttranslational m...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.37.1.143

    authors: Gibbs JB,Oliff A

    更新日期:1997-01-01 00:00:00

  • Tissue renin-angiotensin-aldosterone systems: Targets for pharmacological therapy.

    abstract::The renin-angiotensin-aldosterone system is one of the most important systems in cardiovascular control and in the pathogenesis of cardiovascular diseases. Therefore, it is already a very successful drug target for the therapy of these diseases. However, angiotensins are generated not only in the plasma but also local...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.010909.105610

    authors: Bader M

    更新日期:2010-01-01 00:00:00

  • Nuclear Receptors as Therapeutic Targets in Liver Disease: Are We There Yet?

    abstract::Nuclear receptors (NR) are ligand-modulated transcription factors that play diverse roles in cell differentiation, development, proliferation, and metabolism and are associated with numerous liver pathologies such as cancer, steatosis, inflammation, fibrosis, cholestasis, and xenobiotic/drug-induced liver injury. The ...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-010715-103209

    authors: Rudraiah S,Zhang X,Wang L

    更新日期:2016-01-01 00:00:00

  • Mechanism-based pharmacokinetic-pharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysis.

    abstract::Mechanism-based PK-PD models differ from conventional PK-PD models in that they contain specific expressions to characterize, in a quantitative manner, processes on the causal path between drug administration and effect. This includes target site distribution, target binding and activation, pharmacodynamic interaction...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.47.120505.105154

    authors: Danhof M,de Jongh J,De Lange EC,Della Pasqua O,Ploeger BA,Voskuyl RA

    更新日期:2007-01-01 00:00:00

  • Autophagy in toxicology: cause or consequence?

    abstract::Research on autophagy and its effects on cell metabolism and physiology has increased dramatically during recent years. Multiple forms of autophagy have been characterized, and many of the genes involved in the regulation of this process have been identified. The importance of autophagy for embryonic development and m...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-011112-140210

    authors: Orrenius S,Kaminskyy VO,Zhivotovsky B

    更新日期:2013-01-01 00:00:00

  • The Conducted Vasomotor Response: Function, Biophysical Basis, and Pharmacological Control.

    abstract::Arterial tone is coordinated among vessel segments to optimize nutrient transport and organ function. Coordinated vasomotor activity is remarkable to observe and depends on stimuli, sparsely generated in tissue, eliciting electrical responses that conduct lengthwise among electrically coupled vascular cells. The condu...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-010617-052623

    authors: Welsh DG,Tran CHT,Hald BO,Sancho M

    更新日期:2018-01-06 00:00:00

  • Circadian rhythms: mechanisms and therapeutic implications.

    abstract::The mammalian circadian system is organized in a hierarchical manner in that a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's hypothalamus synchronizes cellular circadian oscillators in most peripheral body cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major timing cue...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.47.120505.105208

    authors: Levi F,Schibler U

    更新日期:2007-01-01 00:00:00

  • Novel Clinical Toxicology and Pharmacology of Organophosphorus Insecticide Self-Poisoning.

    abstract::Organophosphorus insecticide self-poisoning is a major global health problem, killing over 100,000 people annually. It is a complex multi-organ condition, involving the inhibition of cholinesterases, and perhaps other enzymes, and the effects of large doses of ingested solvents. Variability between organophosphorus in...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-010818-021842

    authors: Eddleston M

    更新日期:2019-01-06 00:00:00

  • Pharmacology of Antisense Drugs.

    abstract::Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and hav...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-pharmtox-010716-104846

    authors: Bennett CF,Baker BF,Pham N,Swayze E,Geary RS

    更新日期:2017-01-06 00:00:00

  • Effects of drugs on the electrical activity of the brain: anesthetics.

    abstract::The major concepts presented in this review can be summarized as follows: 1. There is a multidirectional continuum of anesthetic states--some represented by CNS excitation and others by depression. 2. The reticular activating system is influenced by all anesthetics; some inhibit its action (stage III) and some hyperex...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pa.16.040176.002213

    authors: Winters WD

    更新日期:1976-01-01 00:00:00

  • Structure and function of the beta 3-adrenergic receptor.

    abstract::The beta 3 subtype of adrenaline and noradrenaline receptors has now been extensively characterized at the structural and functional levels. Ligand binding and adenylyl cyclase activation studies helped define a beta-adrenergic profile that is quite distinct from that of the beta 1- and beta 2-adrenergic receptors, bu...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.37.1.421

    authors: Strosberg AD

    更新日期:1997-01-01 00:00:00

  • Retinoid receptors and their coregulators.

    abstract::Retinoids regulate gene transcription by binding to the nuclear receptors, the retinoic acid (RA) receptors (RARs), and the retinoid X receptors (RXRs). RARs and RXRs are ligand-activated transcription factors for the regulation of RA-responsive genes. The actions of RARs and RXRs on gene transcription require a highl...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.43.100901.140301

    authors: Wei LN

    更新日期:2003-01-01 00:00:00

  • Transgenic animal models for detection of in vivo mutations.

    abstract::Transgenic rodent models for measuring mutations provide a tool for assessing tissue-specific mutations following in vivo treatment. These systems are based on the insertion into the rodent genome Escherichia coli lacI (lac repressor) or lacZ (beta-galactosidase) genes that serve as targets for mutations. Following in...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pa.35.040195.001045

    authors: Mirsalis JC,Monforte JA,Winegar RA

    更新日期:1995-01-01 00:00:00

  • The role of calpain in oncotic cell death.

    abstract::Numerous lines of evidence demonstrate that calpains, a family of 14 Ca(2+)-activated neutral cysteine proteases, are involved in oncotic cell death in a variety of models. At this time, the biochemistry of most calpains and the specific roles of different calpains in physiology and pathology remain to be determined. ...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.44.101802.121804

    authors: Liu X,Van Vleet T,Schnellmann RG

    更新日期:2004-01-01 00:00:00

  • Cytochrome P450 activation of arylamines and heterocyclic amines.

    abstract::Arylamines and heterocyclic arylamines (HAAs) are of particular interest because of demonstrated carcinogenicity in animals and humans and the broad exposure to many of these compounds. The activation of these, and also some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 (P450). P450 1A2 plays a...

    journal_title:Annual review of pharmacology and toxicology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.pharmtox.45.120403.100010

    authors: Kim D,Guengerich FP

    更新日期:2005-01-01 00:00:00