Transgenic animal models for detection of in vivo mutations.

abstract：:Drug transporters are now widely acknowledged as important determinants governing drug absorption, excretion, and, in many cases, extent of drug entry into target organs. There is also a greater appreciation that altered drug transporter function, whether due to genetic polymorphisms, drug-drug interactions, or enviro...

journal_title：Annual review of pharmacology and toxicology

authors： DeGorter MK,Xia CQ,Yang JJ,Kim RB

更新日期：2012-01-01 00:00:00

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

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

更新日期：2014-01-01 00:00:00

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

authors： Gibbs JB,Oliff A

更新日期：1997-01-01 00:00:00

abstract：:The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production that in turn guides cell growth and proliferation. Cancer cells commonly harbor mutations that ina...

journal_title：Annual review of pharmacology and toxicology

authors： Drygin D,Rice WG,Grummt I

更新日期：2010-01-01 00:00:00

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 facilit...

journal_title：Annual review of pharmacology and toxicology

authors： Patel HH,Murray F,Insel PA

更新日期：2008-01-01 00:00:00

abstract：:Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered inter...

journal_title：Annual review of pharmacology and toxicology

authors： Vermeij WP,Hoeijmakers JH,Pothof J

更新日期：2016-01-01 00:00:00

abstract：:Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are two Ca(2+) messengers derived from NAD and NADP, respectively. Although NAADP is a linear molecule, structurally distinct from the cyclic cADPR, it is synthesized by similar enzymes, ADP-ribosyl cyclase and its homolog, CD38. The c...

journal_title：Annual review of pharmacology and toxicology

authors： Lee HC

更新日期：2001-01-01 00:00:00

abstract：:Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme ...

journal_title：Annual review of pharmacology and toxicology

authors： Insel PA,Amara SG,Blaschke TF,Meyer UA

更新日期：2017-01-06 00:00:00

abstract：:CB1 and CB2 cannabinoid receptors are the primary targets of endogenous cannabinoids (endocannabinoids). These G protein-coupled receptors play an important role in many processes, including metabolic regulation, craving, pain, anxiety, bone growth, and immune function. Cannabinoid receptors can be engaged directly by...

journal_title：Annual review of pharmacology and toxicology

authors： Mackie K

更新日期：2006-01-01 00:00:00

abstract：:The promise of drug repurposing is to accelerate the translation of knowledge to treatment of human disease, bypassing common challenges associated with drug development to be more time- and cost-efficient. Repurposing has an increased chance of success due to the previous validation of drug safety and allows for the ...

journal_title：Annual review of pharmacology and toxicology

authors： Pulley JM,Rhoads JP,Jerome RN,Challa AP,Erreger KB,Joly MM,Lavieri RR,Perry KE,Zaleski NM,Shirey-Rice JK,Aronoff DM

更新日期：2020-01-06 00:00:00

abstract：:Neuroglial cells of the central nervous system include the astrocytes, oligodendrocytes, and microglia. Their counterparts in the peripheral nervous system are the Schwann cells. The term neuroglia comes from an erroneous concept originally coined by Virchow (1850), in which he envisioned the neurons to be embedded in...

journal_title：Annual review of pharmacology and toxicology

authors： Aschner M,Allen JW,Kimelberg HK,LoPachin RM,Streit WJ

更新日期：1999-01-01 00:00:00

abstract：:Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK) kinase kinase of the c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. ASK1 is preferentially activated by various cytotoxic stressors and plays pivotal roles in a wide variety of cellular response to them. Recent analyses of A...

journal_title：Annual review of pharmacology and toxicology

authors： Takeda K,Noguchi T,Naguro I,Ichijo H

更新日期：2008-01-01 00:00:00

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

authors： Eddleston M

更新日期：2019-01-06 00:00:00

abstract：:The application of rapid methods currently used for screening discovery drug candidates for metabolism and pharmacokinetic characteristics is discussed. General considerations are given for screening in this context, including the criteria for good screens, the use of counterscreens, the proper sequencing of screens, ...

journal_title：Annual review of pharmacology and toxicology

authors： White RE

更新日期：2000-01-01 00:00:00

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

authors： Bevan JA,Henrion D

更新日期：1994-01-01 00:00:00

abstract：:Conflicting views abound on the peripheral neurotransmitter and neuromodulator roles of purine compounds. Substantial organ- and species-related variations have become apparent. There is, however, a body of compelling evidence for such roles, if not so broad and ubiquitous as those envisioned (7) for the central nervo...

journal_title：Annual review of pharmacology and toxicology

authors： Su C

更新日期：1983-01-01 00:00:00

abstract：:In this review, we discuss the potential pharmacological targeting of a set of powerful epigenetic mechanisms: DNA methylation control systems in the central nervous system (CNS). Specifically, we focus on the possible use of these targets for novel future treatments for learning and memory disorders. We first describ...

journal_title：Annual review of pharmacology and toxicology

authors： Day JJ,Kennedy AJ,Sweatt JD

更新日期：2015-01-01 00:00:00

abstract：:Though opioid receptors are more difficult to purify and characterize than other cell surface receptors, significant progress has been made in the past several years. At least a dozen groups have now reported purification of opioid-binding proteins, either in a form that retains ligand-binding properties, or in a cova...

journal_title：Annual review of pharmacology and toxicology

authors： Loh HH,Smith AP

更新日期：1990-01-01 00:00:00

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

authors： Levi F,Schibler U

更新日期：2007-01-01 00:00:00

abstract：:Development of scientific creativity is often tied closely to mentorship. In my case, two years with Julius Axelrod, the sum total of my research training, was transformative. My mentoring generations of graduate students and postdoctoral fellows has been as nurturing for me as it has been for them. Work in our lab ov...

journal_title：Annual review of pharmacology and toxicology

authors： Snyder SH

更新日期：2017-01-06 00:00:00

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

authors： Orrenius S,Kaminskyy VO,Zhivotovsky B

更新日期：2013-01-01 00:00:00

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

authors： Rudraiah S,Zhang X,Wang L

更新日期：2016-01-01 00:00:00

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

authors： Wei LN

更新日期：2003-01-01 00:00:00

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

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

更新日期：2018-01-06 00:00:00

abstract：:The theme "New Approaches for Studying Drug and Toxicant Action: Applications to Drug Discovery and Development" links 13 articles in this volume of the Annual Review of Pharmacology and Toxicology (ARPT). The engaging prefatory articles by Arthur Cho and Robert Lefkowitz set the stage for this theme and for the revie...

journal_title：Annual review of pharmacology and toxicology

authors： Insel PA,Amara SG,Blaschke TF,Meyer UA

更新日期：2018-01-06 00:00:00

abstract：:Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included...

journal_title：Annual review of pharmacology and toxicology

authors： Vane JR,Bakhle YS,Botting RM

更新日期：1998-01-01 00:00:00

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

authors： Casida JE

更新日期：2017-01-06 00:00:00

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

authors： Kim D,Guengerich FP

更新日期：2005-01-01 00:00:00

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

authors： Stout SC,Owens MJ,Nemeroff CB

更新日期：2001-01-01 00:00:00

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

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

更新日期：2017-01-06 00:00:00