Abstract
Intermedin/adrenomedullin-2 (IMD/AM2) belongs to the calcitonin gene-related peptide (CGRP) / adrenomedullin (AM) family. The biological actions of this family are attributed to their actions at three receptor subtypes comprising the calcitonin receptor-like receptor (CLR) complexed with one of three receptor activity modifying proteins. In contrast to AM and CGRP, IMD binds non-selectively to all three receptor subtypes: CGRP, AM1, AM2. The peptide displays an overlapping but differential and more restricted distribution across the healthy systemic and pulmonary vasculature, heart and kidney relative to CGRP and AM. This, combined with tissue, regional and cell-type specific receptor expression, underpins differences in regard to magnitude, potency and duration of haemodynamic, cardiac and renal effects of IMD relative to those of AM and CGRP, and receptor-subtype involvement. In common with other family members, IMD protects the mammalian vasculature, myocardium and kidney from acute ischaemia-reperfusion injury, chronic oxidative stress and pressure-loading; IMD inhibits apoptosis, attenuates maladaptive tissue remodelling and preserves cardiac and renal function. Robust upregulation of IMD expression in rodent models of cardiovascular and renal disease argues strongly for the pathophysiological relevance of this particular counter-regulatory peptide. Such findings are likely to translate well to the clinic: early reports indicate that IMD is expressed in and protects cultured human vascular and cardiac non-vascular cells from simulated ischaemia-reperfusion injury, primarily via the AM1 receptor, and may have utility as a plasma biomarker in cardiovascular disease. These observations should provide the rationale for short-term administration of the peptide in acute disease, including myocardial infarction, cerebrovascular insult, cardiac and renal failure.
Keywords: Adrenomedullin, CGRP, heart, hypertrophy, intermedin/adrenomedullin-2, ischaemia-reperfusion, kidney, oxidative stress.
Current Protein & Peptide Science
Title:Protective Effects of Intermedin On Cardiovascular, Pulmonary and Renal Diseases: Comparison with Adrenomedullin and CGRP
Volume: 14 Issue: 4
Author(s): David Holmes, Malcolm Campbell, Mark Harbinson and David Bell
Affiliation:
Keywords: Adrenomedullin, CGRP, heart, hypertrophy, intermedin/adrenomedullin-2, ischaemia-reperfusion, kidney, oxidative stress.
Abstract: Intermedin/adrenomedullin-2 (IMD/AM2) belongs to the calcitonin gene-related peptide (CGRP) / adrenomedullin (AM) family. The biological actions of this family are attributed to their actions at three receptor subtypes comprising the calcitonin receptor-like receptor (CLR) complexed with one of three receptor activity modifying proteins. In contrast to AM and CGRP, IMD binds non-selectively to all three receptor subtypes: CGRP, AM1, AM2. The peptide displays an overlapping but differential and more restricted distribution across the healthy systemic and pulmonary vasculature, heart and kidney relative to CGRP and AM. This, combined with tissue, regional and cell-type specific receptor expression, underpins differences in regard to magnitude, potency and duration of haemodynamic, cardiac and renal effects of IMD relative to those of AM and CGRP, and receptor-subtype involvement. In common with other family members, IMD protects the mammalian vasculature, myocardium and kidney from acute ischaemia-reperfusion injury, chronic oxidative stress and pressure-loading; IMD inhibits apoptosis, attenuates maladaptive tissue remodelling and preserves cardiac and renal function. Robust upregulation of IMD expression in rodent models of cardiovascular and renal disease argues strongly for the pathophysiological relevance of this particular counter-regulatory peptide. Such findings are likely to translate well to the clinic: early reports indicate that IMD is expressed in and protects cultured human vascular and cardiac non-vascular cells from simulated ischaemia-reperfusion injury, primarily via the AM1 receptor, and may have utility as a plasma biomarker in cardiovascular disease. These observations should provide the rationale for short-term administration of the peptide in acute disease, including myocardial infarction, cerebrovascular insult, cardiac and renal failure.
Export Options
About this article
Cite this article as:
Holmes David, Campbell Malcolm, Harbinson Mark and Bell David, Protective Effects of Intermedin On Cardiovascular, Pulmonary and Renal Diseases: Comparison with Adrenomedullin and CGRP, Current Protein & Peptide Science 2013; 14 (4) . https://dx.doi.org/10.2174/13892037113149990049
DOI https://dx.doi.org/10.2174/13892037113149990049 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
Antioxidant Effects of Coumarins Include Direct Radical Scavenging, Metal Chelation and Inhibition of ROS-Producing Enzymes
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: Cardio-Metabolic Complications: Current Perspective and Future Developments)
Current Pharmaceutical Design Regulatory Role of Anesthetics on Heme Oxygenase-1
Current Drug Targets Mutagenic Approaches to Modifying Gap Junction Phenotype
Current Drug Targets Fructose 1,6-Bisphosphate: A Summary of Its Cytoprotective Mechanism
Current Medicinal Chemistry Surfactant Protein (SP)-A and SP-D as Antimicrobial and Immunotherapeutic Agents
Recent Patents on Anti-Infective Drug Discovery Therapeutic Use of Nitric Oxide Scavengers in Shock and Sepsis
Current Pharmaceutical Design Relevance of the Vascular Effects of Insulin in the Rationale of its Therapeutical Use
Cardiovascular & Hematological Disorders-Drug Targets Ca2+ Signalling in Damaged Endothelium and Arterial Remodelling: Do Connexin Hemichannels Provide a Suitable Target to Prevent In-stent Restenosis?
Current Drug Therapy Implications of Epigenetic Mechanisms and their Targets in Cerebral Ischemia Models
Current Neuropharmacology Therapeutic Effects of Micronutrient Supplements on Sperm Parameters: Fact or Fiction?
Current Pharmaceutical Design Phytochemical Genistein in the Regulation of Vascular Function: New Insights
Current Medicinal Chemistry Sida cordifolia, a Traditional Herb in Modern Perspective – A Review
Current Traditional Medicine Commentary-1 Research Highlights (Never Underestimate the Power of Adenosine in Multiple Sclerosis)
CNS & Neurological Disorders - Drug Targets Increasing Bcl-2 and Neuroglubin Expression in Hypoxic Hippocampal Neurons under Hypoxia Preconditioning and in 3-n-butylphalide Treated Cells under Oxygen Glucose Deprivation/Reoxygenation
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Antioxidant Therapy in Alzheimers Disease: Theory and Practice
Mini-Reviews in Medicinal Chemistry Inflammation and Thrombophilia in Pregnancy Complications: Implications for Risk Assessment and Clinical Management
Cardiovascular & Hematological Disorders-Drug Targets IL-1 Cytokines in Cardiovascular Disease: Diagnostic, Prognostic and Therapeutic Implications
Cardiovascular & Hematological Agents in Medicinal Chemistry Modulation of Cardiac and Hepatic Cytochrome P450 Enzymes During Heart Failure
Current Drug Metabolism Targeting Extracellular Matrix Proteolysis for Hemorrhagic Complications of tPA Stroke Therapy
CNS & Neurological Disorders - Drug Targets