Download or read book Functional Selectivity of G Protein Coupled Receptor Ligands written by Kim Neve and published by Springer Science & Business Media. This book was released on 2009-02-27 with total page 290 pages. Available in PDF, EPUB and Kindle. Book excerpt: Functional selectivity refers to the ability of different ligands acting at one receptor subtype to activate multiple signaling pathways in unique combinations; that is, one drug can be an agonist at pathway A and an antagonist or partial agonist at pathway B, and another drug can have the reverse profile. Functional selectivity has profound implications for drug development, for chemical biology, and for the design of experiments to characterize receptor function. In Functional Selectivity of G Protein-Coupled Receptors expert neuroscientists and pharmacologists review the work that demonstrated the existence of functional selectivity, placed it within a theoretical framework, and provided a mechanistic basis for the phenomenon. This exciting, comprehensive, and future-oriented volume includes chapters that focus on theoretical and mechanistic aspects of functional selectivity and that cut across subfamilies of GPCRs. Additional chapters focus on subfamilies of therapeutically relevant receptors where there is considerable evidence of ligand functional selectivity. Accessible and authoritative, Functional Selectivity of G Protein-Coupled Receptors is a valuable educational tool and reference source for students and scientists interested in drug development, chemical biology, and GPCR function.
Download or read book Functional Selectivity and Desensitisation of G Protein coupled Receptors written by Jamie Lorcan McPherson and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The existence of functional selectivity at the mu-opioid receptor was examined by determining the efficacy of a range of opioid agonists for promoting G protein activation and arrestin-3 translocation. In general, there is a good correlation between the efficacy of an opioid agonist at promoting G protein signaling, and the efficacy at recruiting arrestin-3 to the receptor. Endomorphin 2 appears to be an example of a biased ligand with significantly higher efficacy for arrestin-3 translocation, while morphine does not appear to be biased. The kinetics of binding for DAMGO, morphine and endomorphin 2 were determined by competition kinetic assay as a potential explanation for the apparent bias of endomorphin 2. Mean occupancy times of DAMGO, endomorphin 2 and morphine at MOPr are similar to the time required for GRK2-mediated phosphorylation, indicating that kinetics of binding may be a determinant of their ability to promote arrestin-3 signaling at MOPr. The abilities of DAMGO, morphine and endomorphin 2 to induce desensitization of GIRK currents in AtT-20 cells expressing wild type mu-opioid receptor, mu-opioid receptor containing S261/363A substitutions, and mu-opioid receptor with a C terminal truncation from amino acid 354-398 were examined. From the results, it appears that agonist-induced acute desensitization in AtT-20 cells has multiple components. C terminal truncation of MOPr resulted in a slight inhibition of endomorphin 2-induced desensitization. Alanine substitution at serine 261 and 363 inhibited desensitization induced by endomorphin 2. Treatment with the GRK2 inhibitor 5-[2-(5-nitro-2- furyl)vinyl]-2-furoate slightly but significantly inhibited desensitization induced by DAMGO, and to a very small extent morphine, but not endomorph in 2, which may indicate that biased ligands trigger receptor regulation in a different manner to unbiased ligands.
Download or read book G Protein Coupled Receptors written by Tatsuya Haga and published by CRC Press. This book was released on 2005-08-04 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a broad base of knowledge of G-protein-coupled receptors. Useful at both the university and industrial levels, this book is of particular interest to those who are developing therapeutic approaches to diseases using drugs that influence receptor activation.
Download or read book Use of Cellular Impedance to Characterize Ligand Functional Selectivity at G Protein coupled Receptors written by Wayne Stallaert and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book G Protein Signaling written by Alan V. Smrcka and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alan V. Smrcka presents a collection of cutting-edge methods for investigating G protein signaling from a variety of perspectives ranging from in vitro biochemistry to whole animal studies. Among the readily reproducible techniques presented are those for the purification of G proteins and effectors enzymes, assays of these purified G proteins and effector enzymes, and for the study of G proteins interactions with effectors in intact cells. Additional methods are provided for assaying G protein coupled receptor structure, function, and localization, and for studying the physiological roles for endogenous G proteins.
Download or read book The G Protein Coupled Receptors Handbook written by Lakshmi A. Devi and published by Springer Science & Business Media. This book was released on 2008-03-01 with total page 414 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive survey of the many recent advances in the field of G protein-coupled receptors (GPCR). The authors describe the current knowledge of GPCR receptor structure and function, the different mechanisms involved in the regulation of GPCR function, and the role of pharmacological chaperones in GPCR folding and maturation. They also present new findings about how GPCR dimerization/oligomerization modifies the properties of individual receptors and show how recent developments are leading to significant advances in drug discovery, such as the detection of ligands for orphan GPCRs. Also discussed are the most recent developments that could lead to new drug discoveries: the role of GPCRs in mediating pain, the development of receptor-type selective drugs based on the structural plasticity of receptor activation, and the identification of natural ligands of orphan GPCRs (deorphanization) as possible drug targets.
Download or read book Pharmacology of G Protein Coupled Receptors written by Richard R. Neubig and published by Academic Press. This book was released on 2011-09-19 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: G protein coupled receptors remain the most important class of therapeutic targets in medicine. In the last 5 years, tremendous advances have been made in our understanding of the structure and mechanism of this critical family of drug targets. The present volume explores the modern experimental and conceptual framework for drug discovery for G protein coupled receptors. It explores advances in structure determination and structure-based drug design as well as new concepts of allosteric modulation, functional selectivity/biased agonism, and pharmacological chaperones. In addition, emerging drug targets such as receptor families for fatty acids, carboxylic acids, lipid mediators, etc. are included. Final chapters cover novel mechanisms of signal regulation through PDZ domains and RGS proteins. This volume will bring an up-to-date perspective on the G protein coupled receptor field to both academic and industry scientists. The present volume explores the modern experimental and conceptual framework for drug discovery for G protein coupled receptors It explores advances in structure determination and structure-based drug design as well as new concepts of allosteric modulation, functional selectivity/biased agonism, and pharmacological chaperones This volume will bring an up-to-date perspective on the G protein coupled receptor field to both academic and industry scientists
Download or read book Biased Signaling in Physiology Pharmacology and Therapeutics written by Brian J Arey and published by Elsevier. This book was released on 2014-06-05 with total page 317 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biased Signaling in Physiology, Pharmacology and Therapeutics is a unique and essential reference for the scientific community concerning how conformational-dependent activation is a common phenomenon across many classes of receptors or signaling molecules. It discusses the role of conformational dynamics in leading to signaling bias across different classes of receptors and signaling molecules. By providing a broader view of signaling bias, this resource helps to explain common mechanisms shared across receptor classes and how this can be utilized to elucidate their cellular activity and better understand their therapeutic potential. Written for both new and established scientists in pharmacology, cell biology, biochemistry, and signal transduction, as well as physicians, this book clearly illustrates how biased receptor signaling can be utilized to develop and understand complex pharmacology. Chapters are each focused on a specific class of receptor or other important topic and make use of real-world examples illustrating how the latest research in signal transduction has led to a better understanding of pharmacology and cell biology. This structure creates a basis for understanding that physiological signalling bias has been selected by nature in order to provide complex and tissue- specific biological responses in the face of limited receptors and signaling pathways. This book provides a framework to reveal that these physiological mechanisms are not restricted to one receptor type or family and thus presents receptor signaling from a newer, more global perspective. - Offers a unique and valuable resource on biased receptor signaling that provides a global view for better understanding pharmacology across many receptor families - Integrates biased receptor signaling, physiology, and pharmacology to place this emerging science within the context of treating disease - Includes important chapters on both the pharmaceutical and therapeutic implications of biased signaling
Download or read book Serotonin Receptors in Neurobiology written by Amitabha Chattopadhyay and published by CRC Press. This book was released on 2007-05-17 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt: A number of developments spanning a multitude of techniques makes this an exciting time for research in serotonin receptors. A comprehensive review of the subject from a multidisciplinary perspective, Serotonin Receptors in Neurobiology is among the first books to include information on serotonin receptor knockout studies. With contributions from l
Download or read book G Protein Coupled Receptors written by Jesus Giraldo and published by Royal Society of Chemistry. This book was released on 2011-08-16 with total page 549 pages. Available in PDF, EPUB and Kindle. Book excerpt: G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors, with more than 800 members identified thus far in the human genome. They regulate the function of most cells in the body, and represent approximately 3% of the genes in the human genome. These receptors respond to a wide variety of structurally diverse ligands, ranging from small molecules, such as biogenic amines, nucleotides and ions, to lipids, peptides, proteins, and even light. Ligands (agonists and antagonists) acting on GPCRs are important in the treatment of numerous diseases, including cardiovascular and mental disorders, retinal degeneration, cancer, and AIDS. It is estimated that these receptors represent about one third of the actual identified targets of clinically used drugs. The determination of rhodopsin crystal structure and, more recently, of opsin, 1 and 2 adrenergic and A2A adenosine receptors provides both academia and industry with extremely valuable data for a better understanding of the molecular determinants of receptor function and a more reliable rationale for drug design. GPCR structure and function constitutes a hot topic. The book, which lies between the fields of chemical biology, molecular pharmacology and medicinal chemistry, is divided into three parts. The first part considers what receptor structures tell us about the mechanism of receptor activation. Part II focuses on receptor function. It discusses what the data from biophysical and mutational studies, and the analysis of the interactions of the receptor with ligands and regulator proteins, tell us about the process of signal transduction. The final part, on modelling and simulation, details new insights on the link between structure and mechanism and their implications in drug design.
Download or read book Receptor Receptor Interactions written by Kjell Fuxe and published by Springer Science & Business Media. This book was released on 2013-03-13 with total page 577 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book G Protein Coupled Receptor Signaling written by Mario Tiberi and published by Humana Press. This book was released on 2019-03-01 with total page 406 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed volume assembles comprehensive protocols to assist with the study of structural, molecular, cell biological, and in vivo facets of GPCRs, and to enable the development of experimental tools for screening novel GPCR drugs. Sections explore the tweaking of ligands, bioluminescence and FRET approaches, specific GPCR signaling properties, as well as visualization of subcellular compartmentalization. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, G Protein-Coupled Receptor Signaling: Methods and Protocols serves as an ideal reference for life scientists working in a variety of research fields including molecular pharmacology, cell and developmental biology, brain behavior and physiology, drug development and screening. Chapter 4 is available open access under a CC BY 4.0 license via link.springer.com.
Download or read book A Functional Selectivity Mechanism at the Serotonin 2A GPCR Involves Ligand dependent Conformations of Intracellular Loop 2 written by and published by . This book was released on 2014 with total page 11 pages. Available in PDF, EPUB and Kindle. Book excerpt: With recent progress in determination of G protein-coupled receptor (GPCR) structure with crystallography, a variety of other experimental approaches (e.g., NMR spectroscopy, fluorescent-based assays, mass spectrometry techniques) are also being used to characterize state-specific and ligand-specific conformational states. MD simulations offer a powerful complementary approach to elucidate the dynamic features associated with ligand-specific GPCR conformations. To shed light on the conformational elements and dynamics of the important aspect of GPCR functional selectivity, we carried out unbiased microsecond-length MD simulations of the human serotonin 2A receptor (5-HT2AR) in the absence of ligand and bound to four distinct serotonergic agonists. The 5-HT2AR is a suitable system to study the structural features involved in the ligand-dependent conformational heterogeneity of GPCRs because it is well-characterized experimentally and exhibits a strong agonist-specific phenotype in that some 5-HT2AR agonists induce LSD-like hallucinations, while others lack this psychoactive property entirely. Here we report evidence for structural and dynamic differences in 5-HT2AR interacting with such pharmacologically distinct ligands, hallucinogens, and nonhallucinogens obtained from all-atom MD simulations. Differential ligand binding contacts were identified for structurally similar hallucinogens and nonhallucinogens and found to correspond to different conformations in the intracellular loop 2 (ICL2). From the different ICL2 conformations, functional selective phenotypes are suggested through effects on dimerization and/or distinct direct interaction with effector proteins. Lastly, the findings are presented in the context of currently proposed hallucinogenesis mechanisms, and ICL2 is proposed as a fine-tuning selective switch that can differentiates modes of 5-HT2AR activation.
Download or read book Ligand Design for G Protein coupled Receptors Volume 30 written by Didier Rognan and published by John Wiley & Sons. This book was released on 2006-03-10 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: 1. G protein-coupled receptors in the human genome -- 2. Why G protein-coupled receptors databases are needed -- 3. A novel drug screening assay for G protein-coupled receptors -- 4. Importance of GPCR dimerization for function : the case of the class C GPCRs -- 5. Molecular mechanisms of GPCR activation -- 6. Allosteric properties and regulation of G protein-coupled receptors -- 7. Chemogenomics approaches to ligand design -- 8. Strategies for the design of pGPCR-targeted libraries -- 9. Ligand-based rational design : virtual screening -- 10. 3-D structure of G protein-coupled receptors --11. 7TM models in structure-based drug design -- 12. Receptor-based rational design : virtual screening.
Download or read book Principles of Endocrinology and Hormone Action written by Antonino Belfiore and published by Springer. This book was released on 2018-02-08 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides comprehensive coverage of the current knowledge of the physiology of the endocrine system and hormone synthesis and release, transport, and action at the molecular and cellular levels. It presents essential as well as in-depth information of value to both medical students and specialists in Endocrinology, Gynecology, Pediatrics, and Internal Medicine. Although it is well established that the endocrine system regulates essential functions involved in growth, reproduction, and homeostasis, it is increasingly being recognized that this complex regulatory system comprises not only hormones secreted by the classic endocrine glands but also hormones and regulatory factors produced by many organs, and involves extensive crosstalk with the neural and immune system. At the same time, our knowledge of the molecular basis of hormone action has greatly improved. Understanding this complexity of endocrine physiology is crucial to prevent endocrine disorders, to improve the sensitivity of our diagnostic tools, and to provide the rationale for pharmacological, immunological, or genetic interventions. It is such understanding that this book is designed to foster.
Download or read book Molecular Aspects of G Protein coupled Receptors written by Francisco Ciruela and published by Nova Publishers. This book was released on 2008 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the recent years, studies based on two-hybrid screens, proteomic, biochemical and cell biology approaches, have shown that intracellular domains of G protein-coupled receptors (GPCR) or heptaspanning membrane receptors (HSMRs) interact with intracellular proteins. These interactions are the basis of a protein network associated to these receptors which includes scaffolding proteins containing one or several PDZ (post-synaptic density-95, discs large, zona occludens-1) domains, signalling proteins and proteins of the cytoskeleton. The present book is focused on the emerging evidence for interactions of G protein-coupled receptors with scaffolding, cytoskeletal and signalling proteins that will play a role in the targeting, anchoring and functioning of these receptors in the plasma membrane, thus contributing to cell development and plasticity.
Download or read book G Protein Coupled Receptors written by Xinfeng Zhao and published by Springer Nature. This book was released on 2023-02-20 with total page 100 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book summarizes the progress made to functional immobilize G protein-coupled receptors (GPCRs) through site-specific or orientated recognition in both non-covalent and covalent manners. The last decade is the dawn of the “post-structural biology” era for G protein-coupled receptor research. As an emerging approach for state-of-the-art immobilization, this book discusses efforts to explore the elegance of naturally-occurring biochemical reactions by using their high specificity and robust reactivity in the complex system, such as site-specific conjugation by covalent recognition between enzymes and their substrates. With the perspective of protein-drug interactions, this book also reviews the applications of protein immobilization, with an emphasis on G protein-coupled receptors, in drug discovery and protein-ligand interaction analysis. In addition, the merits, opportunities and disadvantages are analyzed for different immobilization methods, and a perspective for future directions is presented. Given its scope, this book appeals to a broad readership, particularly researchers engaged in the field of analytical chemistry, bioconjugate chemistry, and chemical biology, and other related field, as well as teachers of relevant majors in colleges and universities.
