Current Protocols in Pharmacology最新文献_第6页

Rodent Test of Attention and Impulsivity: The 5-Choice Serial Reaction Time Task 啮齿类动物的注意力和冲动性测试:五选择系列反应时间任务

Current Protocols in Pharmacology Pub Date : 2018-02-13 DOI: 10.1002/cpph.27

Guy A. Higgins, Leo B. Silenieks

引用次数: 30

Overview of Monoamine Transporters 单胺转运蛋白综述

Current Protocols in Pharmacology Pub Date : 2018-02-13 DOI: 10.1002/cpph.32

Shaili Aggarwal, Ole V. Mortensen

{"title":"Overview of Monoamine Transporters","authors":"Shaili Aggarwal, Ole V. Mortensen","doi":"10.1002/cpph.32","DOIUrl":"10.1002/cpph.32","url":null,"abstract":"The dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters, which are collectively referred to as monoamine transporters (MATs), play significant roles in regulating the neuronal response to these neurotransmitters. MATs terminate the action of these neurotransmitters by translocating them from the synaptic space into the presynaptic neurons. These three transmitters are responsible for controlling a number of physiological, emotional, and behavioral functions, with their transporters being the site of action of drugs employed for the treatment of a variety of conditions, including depression, anxiety, ADHD, schizophrenia, and psychostimulant abuse. Provided in this unit is information on the localization and regulation of MATs and the structural components of these proteins most responsible for the translocation process. Also included is a brief description of the evolution of ligands that interact with these transporters, as well as current theories concerning the pharmacological effects of substances that interact with these sites, including the molecular mechanisms of action of uptake inhibitors and allosteric modulators. Data relating to the presence, structure, and functions of allosteric modulators are included as well. The aim of this review is to provide background information on MATs to those who are new to this field, with a focus on the therapeutic potential of compounds that interact with these substrate transport sites. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":10871,"journal":{"name":"Current Protocols in Pharmacology","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cpph.32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35674750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 63

All-Optical Electrophysiology for Disease Modeling and Pharmacological Characterization of Neurons 神经元疾病建模和药理表征的全光电生理学

Current Protocols in Pharmacology Pub Date : 2018-02-13 DOI: 10.1002/cpph.25

Christopher A. Werley, Ted Brookings, Hansini Upadhyay, Luis A. Williams, Owen B. McManus, Graham T. Dempsey

{"title":"All-Optical Electrophysiology for Disease Modeling and Pharmacological Characterization of Neurons","authors":"Christopher A. Werley, Ted Brookings, Hansini Upadhyay, Luis A. Williams, Owen B. McManus, Graham T. Dempsey","doi":"10.1002/cpph.25","DOIUrl":"10.1002/cpph.25","url":null,"abstract":"A key challenge for establishing a phenotypic screen for neuronal excitability is measurement of membrane potential changes with high throughput and accuracy. Most approaches for probing excitability rely on low-throughput, invasive methods or lack cell-specific information. These limitations stimulated the development of novel strategies for characterizing the electrical properties of cultured neurons. Among these was the development of optogenetic technologies (Optopatch) that allow for stimulation and recording of membrane voltage signals from cultured neurons with single-cell sensitivity and millisecond temporal resolution. Neuronal activity is elicited using blue light activation of the channelrhodopsin variant ‘CheRiff’. Action potentials and synaptic signals are measured with ‘QuasAr’, a rapid and sensitive voltage-indicating protein with near-infrared fluorescence that scales proportionately with transmembrane potential. This integrated technology of optical stimulation and recording of electrical signals enables investigation of neuronal electrical function with unprecedented scale and precision. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":10871,"journal":{"name":"Current Protocols in Pharmacology","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cpph.25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35391479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 26

Murine Retrovirally-Transduced Bone Marrow Engraftment Models of MLL-Fusion-Driven Acute Myelogenous Leukemias (AML) 逆转录病毒转导的mll融合驱动急性髓性白血病(AML)小鼠骨髓移植模型

Current Protocols in Pharmacology Pub Date : 2018-02-13 DOI: 10.1002/cpph.28

Matthew C. Stubbs, Andrei V. Krivtsov

引用次数: 2

In Vitro Validation of miRNA-Mediated Gene Expression Linked to Drug Metabolism mirna介导的药物代谢相关基因表达的体外验证

Current Protocols in Pharmacology Pub Date : 2018-02-13 DOI: 10.1002/cpph.30

Botros B. Shenoda, Sujay Ramanathan, Seena K. Ajit

{"title":"In Vitro Validation of miRNA-Mediated Gene Expression Linked to Drug Metabolism","authors":"Botros B. Shenoda, Sujay Ramanathan, Seena K. Ajit","doi":"10.1002/cpph.30","DOIUrl":"10.1002/cpph.30","url":null,"abstract":"Pharmacogenomic approaches used to investigate how genes affect drug responses are critical for designing personalized therapies aimed at maximizing efficacy and minimizing adverse effects. Drug efficacy is often dependent on the sequence and expression levels of drug target genes or those involved in the metabolism and transport of the therapeutic agent. Expression of these genes, in turn, is negatively regulated by small noncoding miRNAs. The levels of miRNAs in bodily fluids have been studied extensively as potential diagnostic and prognostic biomarkers. Studies have shown that miRNAs regulate multiple genes and sequence homology is used to predict which genes are subject to regulation by a particular miRNA. Once a gene is identified as a potential target for an miRNA of interest, experiments are undertaken to confirm that the miRNA interacts with the target gene and can alter its level of expression and/or its activity. For example, the differential expression of miRNAs in whole blood obtained from good and poor responders to ketamine has been reported both prior to, and following treatment for complex regional pain syndrome. In this case, hsa-miR-548d-5p was significantly lower in poor responders relative to good responders. This miRNA was predicted to target UDP-glucuronyl transferase 1A1 (UGT1A1), a key drug metabolizing enzyme. Described in this unit are protocols used to confirm miR-548d-5p-mediated UGT1A1 regulation. The approaches described can be employed broadly for the validation of miRNA-mediated negative regulation of any gene. Determining miRNA-mediated regulation of enzymes and transporters affecting drug metabolism is a critical step in designing personalized therapy and for understanding the mechanisms responsible for variations in the responses to therapeutic agents. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":10871,"journal":{"name":"Current Protocols in Pharmacology","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cpph.30","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35674275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Development and Applications of Patient-Derived Xenograft Models in Humanized Mice for Oncology and Immune-Oncology Drug Discovery 用于肿瘤和免疫肿瘤药物开发的人源化小鼠异种移植模型的开发和应用

Current Protocols in Pharmacology Pub Date : 2018-02-13 DOI: 10.1002/cpph.26

Bhavna Verma, Michael Ritchie, Maria Mancini

引用次数: 9

Overview of microRNA Modulation in Analgesic Research 微rna调控在镇痛研究中的应用综述

Current Protocols in Pharmacology Pub Date : 2018-02-13 DOI: 10.1002/cpph.29

Sujay Ramanathan, Botros B. Shenoda, Seena K. Ajit

引用次数: 5

Overview of Transgenic Mouse Models of Myeloproliferative Neoplasms (MPNs). 骨髓增生性肿瘤(mpn)转基因小鼠模型研究综述

Current Protocols in Pharmacology Pub Date : 2017-06-22 DOI: 10.1002/cpph.23

Andrew Dunbar, Abbas Nazir, Ross Levine

{"title":"Overview of Transgenic Mouse Models of Myeloproliferative Neoplasms (MPNs).","authors":"Andrew Dunbar, Abbas Nazir, Ross Levine","doi":"10.1002/cpph.23","DOIUrl":"https://doi.org/10.1002/cpph.23","url":null,"abstract":"Myeloproliferative neoplasms (MPNs) are a class of hematologic diseases characterized by aberrant proliferation of one or more myeloid lineages and progressive bone marrow fibrosis. In 2005, seminal work by multiple groups identified the JAK2V617F mutation in a significant fraction of MPN patients. Since that time, murine models of JAK2V617F have greatly enhanced the understanding of the role of aberrant JAK-STAT signaling in MPN pathogenesis and have provided an in vivo pre-clinical platform that can be used to develop novel therapies. From early retroviral transduction models to transgenics, and ultimately conditional knock-ins, murine models have established that JAK2V617F alone can induce an MPN-like syndrome in vivo. However, additional mutations co-occur with JAK2V617F in MPNs, often in proteins involved in epigenetic regulation that can dramatically influence disease outcomes. In vivo modeling of these mutations in the context of JAK2V617F has provided additional insights into the role of epigenetic dysregulation in augmenting MPN hematopoiesis. In this overview, early murine model development of JAK2V617F is described, with an analysis of its effects on the hematopoietic stem/progenitor cell niche and interactions with downstream signaling elements. This is followed by a description of more recent in vivo models developed for evaluating the effect of concomitant mutations in epigenetic modifiers on MPN maintenance and progression. Mouse models of other driver mutations in MPNs, including primarily calreticulin (CALR) and Tpo-receptor (MPL), which occur in a significant percentage of MPN patients with wild-type JAK2, are also briefly reviewed. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":10871,"journal":{"name":"Current Protocols in Pharmacology","volume":"77 ","pages":"14.40.1-14.40.19"},"PeriodicalIF":0.0,"publicationDate":"2017-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cpph.23","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35111113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

The Ussing Chamber Assay to Study Drug Metabolism and Transport in the Human Intestine. 用腔室法研究药物在人体肠道内的代谢和转运。

Current Protocols in Pharmacology Pub Date : 2017-06-22 DOI: 10.1002/cpph.22

Beatrice Kisser, Eva Mangelsen, Caroline Wingolf, Lars Ivo Partecke, Claus-Dieter Heidecke, Christer Tannergren, Stefan Oswald, Markus Keiser

{"title":"The Ussing Chamber Assay to Study Drug Metabolism and Transport in the Human Intestine.","authors":"Beatrice Kisser, Eva Mangelsen, Caroline Wingolf, Lars Ivo Partecke, Claus-Dieter Heidecke, Christer Tannergren, Stefan Oswald, Markus Keiser","doi":"10.1002/cpph.22","DOIUrl":"https://doi.org/10.1002/cpph.22","url":null,"abstract":"The Ussing chamber is an old but still powerful technique originally designed to study the vectorial transport of ions through frog skin. This technique is also used to investigate the transport of chemical agents through the intestinal barrier as well as drug metabolism in enterocytes, both of which are key determinants for the bioavailability of orally administered drugs. More contemporary model systems, such as Caco-2 cell monolayers or stably transfected cells, are more limited in their use compared to the Ussing chamber because of differences in expression rates of transporter proteins and/or metabolizing enzymes. While there are limitations to the Ussing chamber assay, the use of human intestinal tissue remains the best laboratory test for characterizing the transport and metabolism of compounds following oral administration. Detailed in this unit is a step-by-step protocol for preparing human intestinal tissue, for designing Ussing chamber experiments, and for analyzing and interpreting the findings. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":10871,"journal":{"name":"Current Protocols in Pharmacology","volume":"77 ","pages":"7.17.1-7.17.19"},"PeriodicalIF":0.0,"publicationDate":"2017-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cpph.22","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35111507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Label-Free Dynamic Mass Redistribution and Bio-Impedance Methods for Drug Discovery. 无标签动态质量重分布和生物阻抗方法用于药物发现。

Current Protocols in Pharmacology Pub Date : 2017-06-22 DOI: 10.1002/cpph.24

Manuel Grundmann

{"title":"Label-Free Dynamic Mass Redistribution and Bio-Impedance Methods for Drug Discovery.","authors":"Manuel Grundmann","doi":"10.1002/cpph.24","DOIUrl":"https://doi.org/10.1002/cpph.24","url":null,"abstract":"Label-free biosensors are increasingly employed in drug discovery. Cell-based biosensors provide valuable insights into the biological consequences of exposing cells and tissues to chemical agents and the underlying molecular mechanisms associated with these effects. Optical biosensors based on the detection of dynamic mass redistribution (DMR) and impedance biosensors using cellular dielectric spectroscopy (CDS) capture changes of the cytoskeleton of living cells in real time. Because signal transduction correlates with changes in cell morphology, DMR and CDS biosensors are exquisitely suited for recording integrated cell responses in an unbiased, yet pathway-specific manner without the use of labels that may interfere with cell function. Described in this unit are several experimental approaches utilizing optical label-free system capturing dynamic mass redistribution (DMR) in living cells (Epic System) and an impedance-based CDS technology (CellKey). In addition, potential pitfalls associated with these assays and alternative approaches for overcoming such technical challenges are discussed. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":10871,"journal":{"name":"Current Protocols in Pharmacology","volume":"77 ","pages":"9.24.1-9.24.21"},"PeriodicalIF":0.0,"publicationDate":"2017-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cpph.24","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35111112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8