Download or read book Identifying Novel G Protein coupled Receptor Targets in Pulmonary Hypertension written by Jean Rose Iyinikkel and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Interestingly the CRISPR-GPR75 KO mouse is viable and shows no obvious phenotype. We hypothesise that exposing these CRISPR-GPR75 KO mice to hypoxia will protect them from developing PAH. Taken together our data show the utility of profiling GPCRs in disease and highlight GPCR expression and function could contribute to the sex bias in PAH. We have generated a number of tools that will aide in fully uncovering the pharmacological and physiological role of GPR75. Overall we have validated GPR75 as a novel therapeutic target in PAH; inhibitors of GPR75 would be expected to blunt or reverse remodelling of the pulmonary artery associated with the disease.
Download or read book Identifying Novel G Protein coupled Receptor Targets in Pulmonary Hypertension written by Jean Rose Iyinikkel and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book G Protein coupled Receptor Expression and Function in Pulmonary Artery Smooth Muscle Cells written by Daniel Scott McDonald and published by . This book was released on 2013 with total page 76 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, in part due to increased proliferation of pulmonary artery smooth muscle cells (PASMC). Since the second messenger 3'5'-cyclic adenosine monophosphate (cAMP) decreases proliferation of PASMC, G protein-coupled receptors (GPCRs) that couple to G[alpha]s are attractive targets for PAH. We used a TaqMan® GPCR array to identify the GPCRs expressed by PASMC isolated from normal subjects and from patients with PAH. The data revealed that human PASMC express >135 GPCRs, at least 50 of which regulate cAMP formation. We found that GPCR expression correlates with function e.g., of G[alpha]s-coupled GPCRs with formation of cAMP and inhibition of cell proliferation (a functional response to receptor activation), thus documenting that we had identified physiologically relevant GPCRs. Our studies of PAH-PASMC with GPCR arrays revealed that PAH is associated with an increase (>2-fold) in the expression of 41 GPCRs. The greatest increase in GPCR expression was of two orphan receptors, namely GPR113 and GPR75, whose expression was absent in normal PASMC. We also found the mRNA and protein expression of GPR113 and GPR75 were increased in animal models of PAH. Importantly, treatment of PAH-PASMC with a GPR75 antibody blunted the increased proliferation of PASMC and increased cellular cAMP levels. Taken together, the data in this thesis provide evidence that the GPCR microarray can identify GPCRs that contribute to the physiology of PASMC and can uncover new drug targets, such as GPR75 for PAH--a disease that requires therapies beyond those currently in use.
Download or read book Identification and Expression of G Protein Coupled Receptors written by Kevin R. Lynch and published by Wiley-Liss. This book was released on 1998-03-19 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: The past decade has seen tremendous advances in the study of G protein-coupled receptors (GPCRs), including the molecular cloning and identification of more than 100 GPCR genes. But while GPCRs serve as targets for more than 300 medicines in modern pharmacology, the shrinking pool of known ligands and the continuing discovery of orphan GPCR genes have underscored the need for new approaches for ligand identification. This book addresses this new direction in GPCR biochemistry, offering a definitive laboratory bench manual that emphasizes expression over primary cloning strategies.
Download or read book Identification of Candidate G Protein coupled Receptors written by Gayathri Viswanathan and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification of Candidate G Protein coupled Receptors written by Gayathri Viswanathan and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Regulation of G Protein Coupled Receptor Function and Expression written by Jeffrey L. Benovic and published by Wiley-Liss. This book was released on 1999-11-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent advances in molecular and cell biology enabling the cloning, expression, and mutagenesis of signal transduction proteins has prompted an explosion of knowledge in the field of receptor regulation, facilitating the discovery of new classes of regulatory proteins, and providing a basis and means for manipulating receptor function through multiple intracellular targets. This volume covers methods used to examine how the function(s) of receptors are regulated. Understanding how to regulate the function and expression of these receptors is critical in determining how to modify receptors and to translocating receptors away from the cell surface and its recycling. Individual chapters focus on specific techniques used to characterize receptors (epitope tagging, measurement and analysis of receptor phosphorylation, analysis of the kinetics of receptor desensitization, and assessment of receptor/G protein coupling); the role of regulatory proteins (receptor kinases and phosphatases, arrestins) in modulating receptor function; and the methods used to measure receptor trafficking (ligand binding, immunofluoresence) and expression (transcriptional and translational regulation). * Covers a broad range of important concepts and methodologies which are current in the study of G protein-coupled receptors (GPCRs) * G-protein coupled receptors make up over 40% of the current pharmacological targets * Provides detailed protocols for executing various strategies and offers informed judgments as to what approaches are and aren't useful * Volume Editor, Jeffrey Benovic, is a dominant world leader in the study of receptor regulation of GPCR kinases and is highly respected in the field
Download or read book Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension written by Toshio Nakanishi and published by Springer Nature. This book was released on 2020-02-28 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access book focuses on the molecular mechanism of congenital heart disease and pulmonary hypertension, offering new insights into the development of pulmonary circulation and the ductus arteriosus. It describes in detail the molecular mechanisms involved in the development and morphogenesis of the heart, lungs and ductus arteriosus, covering a range of topics such as gene functions, growth factors, transcription factors and cellular interactions, as well as stem cell engineering technologies. The book also presents recent advances in our understanding of the molecular mechanism of lung development, pulmonary hypertension and molecular regulation of the ductus arteriosus. As such, it is an ideal resource for physicians, scientists and investigators interested in the latest findings on the origins of congenital heart disease and potential future therapies involving pulmonary circulation/hypertension and the ductus arteriosus.
Download or read book G Protein Coupled Receptors in Drug Discovery written by Kenneth H. Lundstrom and published by CRC Press. This book was released on 2005-07-11 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: The broad range of G protein-coupled receptors (GPCRs) encompasses all areas of modern medicine and have an enormous impact on the process of drug development. Using disease-oriented methods to cover everything from screening to expression and crystallization, G Protein-Coupled Receptors in Drug Discovery describes the physiological roles of GPCRs
Download or read book The Endothelium written by Michel Félétou and published by Morgan & Claypool Publishers. This book was released on 2011 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References
Download or read book Pharmacotherapy of Pulmonary Hypertension written by Marc Humbert and published by Springer. This book was released on 2013-10-16 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume focuses on current evidence-based pharmacological treatments of various forms of pulmonary hypertension and provides a comprehensive review of the latest developments in this area. The first part of the book covers the definition, classification, pathophysiology, pathology, biomarkers and animal models of the disease, thus laying the conceptual basis for what follows. The middle section provides an overview of the established therapies, such as calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and inhaled nitric oxide. The last section explores novel pathways and emerging therapeutic approaches including soluble guanylate cyclase stimulators, Rho-kinase inhibitors, inhibitors of serotonin receptors and transporters, peptide growth factors, vasoactive peptides, modulators of redox equilibrium and cyclic nucleotide homeostasis, as well as immunosuppressive and anti-proliferative agents. Particular attention is given to the clinical applications of these experimental therapies, that are on the horizon. The book thus spans the continuum from basic science to clinical applications.
Download or read book Advances in Pulmonary Diseases Cellular Pathology Molecular Targets Novel Diagnosis and Therapy written by Huahao Shen and published by Frontiers Media SA. This book was released on 2022-03-30 with total page 379 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book PanVascular Medicine written by Peter Lanzer and published by Springer. This book was released on 2015-03-30 with total page 5004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vascular management and care has become a truly multidisciplinary enterprise as the number of specialists involved in the treatment of patients with vascular diseases has steadily increased. While in the past, treatments were delivered by individual specialists, in the twenty-first century a team approach is without doubt the most effective strategy. In order to promote professional excellence in this dynamic and rapidly evolving field, a shared knowledge base and interdisciplinary standards need to be established. Pan Vascular Medicine, 2nd edition has been designed to offer such an interdisciplinary platform, providing vascular specialists with state-of-the art descriptive and procedural knowledge. Basic science, diagnostics, and therapy are all comprehensively covered. In a series of succinct, clearly written chapters, renowned specialists introduce and comment on the current international guidelines and present up-to-date reviews of all aspects of vascular care.
Download or read book How Tobacco Smoke Causes Disease written by United States. Public Health Service. Office of the Surgeon General and published by . This book was released on 2010 with total page 728 pages. Available in PDF, EPUB and Kindle. Book excerpt: This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.
Download or read book G Protein Coupled Receptor Kinases GRKs and Beta Arrestins New Insights into Disease Regulators written by Yuichi Hattori and published by Frontiers Media SA. This book was released on 2020-03-10 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Textbook of Pulmonary Vascular Disease written by Jason X. -J. Yuan and published by Springer Science & Business Media. This book was released on 2011-03-24 with total page 1640 pages. Available in PDF, EPUB and Kindle. Book excerpt: Textbook of Pulmonary Vascular Diseases combines basic scientific knowledge on the pulmonary circulatory system at levels of the molecule, cell, tissue, and organ with clinical diagnosis and treatment of pulmonary vascular diseases. State-of-the-art techniques and their potential applications in research, diagnosis, and treatment of pulmonary vascular diseases are also covered.
Download or read book Aldosterone Mineralocorticoid Receptor written by Brian Harvey and published by BoD – Books on Demand. This book was released on 2019-09-25 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is an open access dissemination of the EU COST Action ADMIRE in Aldosterone/Mineralocorticoid Receptor (MR) physiology and pathophysiology. Aldosterone is the major hormone regulating blood pressure. Alterations in blood levels of aldosterone and genetic mutations in the MR receptor are major causes of hypertension and comorbidities. Many of the drugs in clinical use, and in development for treating hypertension, target aldosterone and MR actions in the kidney and cardiovascular system. The ADMIRE book assembles review chapters from 16 European ADMIRE laboratories providing the latest insights into mechanisms of aldosterone synthesis/secretion, aldosterone/MR physiology and signaling, and the pathophysiological roles of aldosterone/MR activation.
