Optical Approaches for Investigating Neuromodulation and G Protein-Coupled Receptor Signaling.

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological Reviews Pub Date : 2023-11-01 Epub Date: 2023-07-10 DOI:10.1124/pharmrev.122.000584
David J Marcus, Michael R Bruchas
{"title":"Optical Approaches for Investigating Neuromodulation and G Protein-Coupled Receptor Signaling.","authors":"David J Marcus, Michael R Bruchas","doi":"10.1124/pharmrev.122.000584","DOIUrl":null,"url":null,"abstract":"<p><p>Despite the fact that roughly 40% of all US Food and Drug Administration (FDA)-approved pharmacological therapeutics target G protein-coupled receptors (GPCRs), there remains a gap in our understanding of the physiologic and functional role of these receptors at the systems level. Although heterologous expression systems and in vitro assays have revealed a tremendous amount about GPCR signaling cascades, how these cascades interact across cell types, tissues, and organ systems remains obscure. Classic behavioral pharmacology experiments lack both the temporal and spatial resolution to resolve these long-standing issues. Over the past half century, there has been a concerted effort toward the development of optical tools for understanding GPCR signaling. From initial ligand uncaging approaches to more recent development of optogenetic techniques, these strategies have allowed researchers to probe longstanding questions in GPCR pharmacology both in vivo and in vitro. These tools have been employed across biologic systems and have allowed for interrogation of everything from specific intramolecular events to pharmacology at the systems level in a spatiotemporally specific manner. In this review, we present a historical perspective on the motivation behind and development of a variety of optical toolkits that have been generated to probe GPCR signaling. Here we highlight how these tools have been used in vivo to uncover the functional role of distinct populations of GPCRs and their signaling cascades at a systems level. SIGNIFICANCE STATEMENT: G protein-coupled receptors (GPCRs) remain one of the most targeted classes of proteins for pharmaceutical intervention, yet we still have a limited understanding of how their unique signaling cascades effect physiology and behavior at the systems level. In this review, we discuss a vast array of optical techniques that have been devised to probe GPCR signaling both in vitro and in vivo.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":null,"pages":null},"PeriodicalIF":19.3000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10595021/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacological Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1124/pharmrev.122.000584","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/7/10 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Despite the fact that roughly 40% of all US Food and Drug Administration (FDA)-approved pharmacological therapeutics target G protein-coupled receptors (GPCRs), there remains a gap in our understanding of the physiologic and functional role of these receptors at the systems level. Although heterologous expression systems and in vitro assays have revealed a tremendous amount about GPCR signaling cascades, how these cascades interact across cell types, tissues, and organ systems remains obscure. Classic behavioral pharmacology experiments lack both the temporal and spatial resolution to resolve these long-standing issues. Over the past half century, there has been a concerted effort toward the development of optical tools for understanding GPCR signaling. From initial ligand uncaging approaches to more recent development of optogenetic techniques, these strategies have allowed researchers to probe longstanding questions in GPCR pharmacology both in vivo and in vitro. These tools have been employed across biologic systems and have allowed for interrogation of everything from specific intramolecular events to pharmacology at the systems level in a spatiotemporally specific manner. In this review, we present a historical perspective on the motivation behind and development of a variety of optical toolkits that have been generated to probe GPCR signaling. Here we highlight how these tools have been used in vivo to uncover the functional role of distinct populations of GPCRs and their signaling cascades at a systems level. SIGNIFICANCE STATEMENT: G protein-coupled receptors (GPCRs) remain one of the most targeted classes of proteins for pharmaceutical intervention, yet we still have a limited understanding of how their unique signaling cascades effect physiology and behavior at the systems level. In this review, we discuss a vast array of optical techniques that have been devised to probe GPCR signaling both in vitro and in vivo.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
研究神经调控和G蛋白偶联受体信号的光学方法。
尽管美国食品药品监督管理局(FDA)批准的所有药物治疗药物中,约有40%针对G蛋白偶联受体(GPCR),但我们对这些受体在系统水平上的生理和功能作用的理解仍存在差距。尽管异源表达系统和体外测定已经揭示了大量关于GPCR信号级联的信息,但这些级联如何在细胞类型、组织和器官系统中相互作用仍然不清楚。经典的行为药理学实验缺乏时间和空间分辨率来解决这些长期存在的问题。在过去的半个世纪里,人们共同致力于开发用于理解GPCR信号的光学工具。从最初的配体解锁方法到光遗传学技术的最新发展,这些策略使研究人员能够在体内和体外探索GPCR药理学中长期存在的问题。这些工具已被应用于整个生物系统,并允许以时空特定的方式在系统水平上询问从特定分子内事件到药理学的一切。在这篇综述中,我们从历史的角度介绍了各种用于探测GPCR信号的光学工具包背后的动机和开发。在这里,我们强调了这些工具是如何在体内使用的,以揭示不同群体的GPCR及其信号级联在系统水平上的功能作用。意义声明:G蛋白偶联受体(GPCR)仍然是药物干预最具针对性的蛋白质类之一,但我们对其独特的信号级联如何在系统水平上影响生理和行为仍有有限的了解。在这篇综述中,我们讨论了一系列用于在体外和体内探测GPCR信号的光学技术。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
期刊最新文献
Ironing Out the Mechanism of gp130 Signaling The 75-Year Anniversary of the Department of Physiology and Pharmacology at Karolinska Institutet—Examples of Recent Accomplishments and Future Perspectives Glatiramer Acetate for the Treatment of Multiple Sclerosis: From First-Generation Therapy to Elucidation of Immunomodulation and Repair How to drug a cloud? Targeting intrinsically disordered proteins. Pharmacological therapies for male infertility.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1