Abstract
Exaggerated activation of the renin-angiotensin system via tissue angiotensin II (Ang II) type 1 receptor (AT1R) signaling exerts detrimental effects on cardiovascular, renal and endocrine systems to provoke hypertension and related target organ damage. On the other hand, accumulated research evidence of both basic and clinical studies shows that physiological AT1R signaling also plays an indispensable role for the normal organ development such as the kidney and the maintenance of cardiovascular and renal homeostasis. Such functional diversity of AT1R signaling prompts us to seek a new strategy of selective modulation of AT1R signaling in pathophysiology. In the course of an investigational search for a means to functionally and selectively modulate AT1R signaling for that purpose, a molecule directly interacting with the carboxyl-terminal cytoplasmic domain of AT1R was identified by employing yeast two-hybrid screening of a mouse kidney cDNA library and named AT1R-associated protein (ATRAP). The results of functional analysis showed that ATRAP promotes constitutive AT1R internalization in cultured cells and inhibits Ang II-mediated pathological response in mouse distal convoluted cells. The ATRAP is expressed in a variety of tissues including the kidney where ATRAP is abundantly distributed in epithelial cells along the renal tubules. The results employing genetic engineered mice with modified ATRAP expression showed that ATRAP plays a key role in the regulation of renal sodium handling and the modulation of blood pressure in response to pathological stimuli such as chronic Ang II infusion, and suggest ATRAP to be a target of interest.
Keywords: Cardiovascular disease, hypertension, kidney, receptor, renal disease, sodium reabsorption.
Current Medicinal Chemistry
Title:Angiotensin II Type 1 Receptor Binding Molecule ATRAP as a Possible Modulator of Renal Sodium Handling and Blood Pressure in Pathophysiology
Volume: 22 Issue: 28
Author(s): K. Tamura, H. Wakui, K. Azushima, K. Uneda, S. Haku, R. Kobayashi, K. Ohki, K. Haruhara, S. Kinguchi, M. Matsuda, A. Yamashita and S. Umemura
Affiliation:
Keywords: Cardiovascular disease, hypertension, kidney, receptor, renal disease, sodium reabsorption.
Abstract: Exaggerated activation of the renin-angiotensin system via tissue angiotensin II (Ang II) type 1 receptor (AT1R) signaling exerts detrimental effects on cardiovascular, renal and endocrine systems to provoke hypertension and related target organ damage. On the other hand, accumulated research evidence of both basic and clinical studies shows that physiological AT1R signaling also plays an indispensable role for the normal organ development such as the kidney and the maintenance of cardiovascular and renal homeostasis. Such functional diversity of AT1R signaling prompts us to seek a new strategy of selective modulation of AT1R signaling in pathophysiology. In the course of an investigational search for a means to functionally and selectively modulate AT1R signaling for that purpose, a molecule directly interacting with the carboxyl-terminal cytoplasmic domain of AT1R was identified by employing yeast two-hybrid screening of a mouse kidney cDNA library and named AT1R-associated protein (ATRAP). The results of functional analysis showed that ATRAP promotes constitutive AT1R internalization in cultured cells and inhibits Ang II-mediated pathological response in mouse distal convoluted cells. The ATRAP is expressed in a variety of tissues including the kidney where ATRAP is abundantly distributed in epithelial cells along the renal tubules. The results employing genetic engineered mice with modified ATRAP expression showed that ATRAP plays a key role in the regulation of renal sodium handling and the modulation of blood pressure in response to pathological stimuli such as chronic Ang II infusion, and suggest ATRAP to be a target of interest.
Export Options
About this article
Cite this article as:
Tamura K., Wakui H., Azushima K., Uneda K., Haku S., Kobayashi R., Ohki K., Haruhara K., Kinguchi S., Matsuda M., Yamashita A. and Umemura S., Angiotensin II Type 1 Receptor Binding Molecule ATRAP as a Possible Modulator of Renal Sodium Handling and Blood Pressure in Pathophysiology, Current Medicinal Chemistry 2015; 22 (28) . https://dx.doi.org/10.2174/0929867322666150821095036
DOI https://dx.doi.org/10.2174/0929867322666150821095036 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
p66 Shc as the Engine of Vascular Aging
Current Vascular Pharmacology Therapeutic Window, a Critical Developmental Stage for Stem Cell Therapies
Current Stem Cell Research & Therapy RNAi in Clinical Studies
Current Medicinal Chemistry Sleep Apnea and Coronary Heart Disease: From Dusk Till Dawn and Further
Current Respiratory Medicine Reviews Hyperhomocysteinemia and Sudden Cardiac Death: Potential Arrhythmogenic Mechanisms
Current Vascular Pharmacology Editorial [ Endothelial Dysfunction: Novel Therapeutic Approaches (Guest Editor: Dimitris Tousoulis)]
Current Vascular Pharmacology Subject Index To Volume 4
Current HIV Research Drug Discovery and Design for Complex Diseases through QSAR Computational Methods
Current Pharmaceutical Design Design and Ocular Tolerance of Flurbiprofen Loaded Nanosuspension
Pharmaceutical Nanotechnology Effects of Pulmonary Blood Flow on Respiratory Mechanics: Measurements by the End-Inflation Occlusion Method in Healthy Rats After Acute Blood Volume Expansion
Current Respiratory Medicine Reviews Lone Atrial Fibrillation- A Diagnosis of Exclusion
Current Pharmaceutical Design Tenofovir-Related Nephropathies in HIV-Infected Patients
Current Vascular Pharmacology Studies on the Effect of the Apolipoprotein E Genotype on the Lipid Profile in Alzheimers Disease
Current Alzheimer Research Pre-eclampsia Versus Cardiovascular Disease Versus CRP
Current Hypertension Reviews Bariatric Surgery - Effects on Obesity and Related co-Morbidities
Current Diabetes Reviews Marine-Derived Bioactive Peptides as New Anticoagulant Agents: A Review
Current Protein & Peptide Science Heat Shock Proteins - Two Sides of a Coin
Current Cardiology Reviews Comparison of Status Epilepticus Models Induced by Pilocarpine and Nerve Agents - A Systematic Review of the Underlying Aetiology and Adopted Therapeutic Approaches
Current Medicinal Chemistry Medical Management of Obesity
Current Nutrition & Food Science The Physiological/Pathophysiological Significance of Vitamin D in Cancer, Cardiovascular Disorders and Beyond
Current Drug Metabolism