Abstract
The most relevant biological action of aldosterone in epithelial tissues is the regulation of sodium reabsorption through binding to the mineralocorticoid receptor (MR). Glucocorticoids also bind with high affinity to MR, which is usually protected by the enzyme 11β-hydroxysteroid dehydrogenase. This activity prevents MR activation by cortisol despite the large prevalence of this steroid in plasma. Nonetheless, there are some aspects of the mechanism of action of MR that are not entirely explained by this competitive metabolic mechanism of protection. The picture is even more complicated in those tissues such as the nervous system where the enzyme is expressed at very low levels or is directly absent in various areas of the brain. Therefore, other cellular and molecular mechanisms must also intervene to allow specific aldosterone biological effects in the presence of overwhelming concentrations of glucocorticoids. In this article, we discuss some possible mechanisms that permit the specificity of action for each type of steroid, including those related to the recently discovered novel molecular mechanism of activation of corticosteroid receptors and the structural requirements of a given ligand to favor the mineralocorticoid action via MR. The relative contribution of these mechanisms may vary in different target cells allowing the fine tuning of cellular functions depending on the degree of cooperation between steroids, receptors, chaperones associated to receptors, and other factors. All these regulatory interactions can be altered in some pathophysiological situations, most of them related to stressing situations.
Keywords: Aldosterone, cortisol, glucocorticoid receptor, heat-shock protein of 90-kDa, immunophilins, mineralocorticoid receptor, stress disorders, steroid conformation.
CNS & Neurological Disorders - Drug Targets
Title:Molecular Basis of Mineralocorticoid Receptor Action in the Nervous System
Volume: 12 Issue: 8
Author(s): Alejandro M. Molinari, Mayra Y. Machado-Rada, Gisela I. Mazaira, Alejandra G. Erlejman and Mario D. Galigniana
Affiliation:
Keywords: Aldosterone, cortisol, glucocorticoid receptor, heat-shock protein of 90-kDa, immunophilins, mineralocorticoid receptor, stress disorders, steroid conformation.
Abstract: The most relevant biological action of aldosterone in epithelial tissues is the regulation of sodium reabsorption through binding to the mineralocorticoid receptor (MR). Glucocorticoids also bind with high affinity to MR, which is usually protected by the enzyme 11β-hydroxysteroid dehydrogenase. This activity prevents MR activation by cortisol despite the large prevalence of this steroid in plasma. Nonetheless, there are some aspects of the mechanism of action of MR that are not entirely explained by this competitive metabolic mechanism of protection. The picture is even more complicated in those tissues such as the nervous system where the enzyme is expressed at very low levels or is directly absent in various areas of the brain. Therefore, other cellular and molecular mechanisms must also intervene to allow specific aldosterone biological effects in the presence of overwhelming concentrations of glucocorticoids. In this article, we discuss some possible mechanisms that permit the specificity of action for each type of steroid, including those related to the recently discovered novel molecular mechanism of activation of corticosteroid receptors and the structural requirements of a given ligand to favor the mineralocorticoid action via MR. The relative contribution of these mechanisms may vary in different target cells allowing the fine tuning of cellular functions depending on the degree of cooperation between steroids, receptors, chaperones associated to receptors, and other factors. All these regulatory interactions can be altered in some pathophysiological situations, most of them related to stressing situations.
Export Options
About this article
Cite this article as:
Molinari M. Alejandro, Machado-Rada Y. Mayra, Mazaira I. Gisela, Erlejman G. Alejandra and Galigniana D. Mario, Molecular Basis of Mineralocorticoid Receptor Action in the Nervous System, CNS & Neurological Disorders - Drug Targets 2013; 12 (8) . https://dx.doi.org/10.2174/187152731131200122
DOI https://dx.doi.org/10.2174/187152731131200122 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Alpha-1 Adrenergic Antagonists Induced Severe Rhinitis in Patients with Benign Prostatic Hyperplasia
Current Drug Safety Multiple Functions of Mammalian Germinal Center Kinases
Current Chemical Biology Regioselective Synthesis of Novel Fused Sulphonamide Derivatives Utilizing Microwave Irradiation
Current Microwave Chemistry Antimicrobial Resistance in the 21st Century: A Multifaceted Challenge
Protein & Peptide Letters The Effect of Adult and Pediatric Cardiopulmonary Bypass on Pharmacokinetic and Pharmacodynamic Parameters
Current Clinical Pharmacology Antenatal Glucocorticoids Supplementation and Central Nervous System Development
Current Drug Metabolism Inflammation and Anemia
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome
Current Neuropharmacology Synthetic Approaches to Heterocyclic Guanidines with Biological Activity: An Update
Current Organic Chemistry An Overview of Non-Neural Sources of Calcitonin Gene-Related Peptide
Current Medicinal Chemistry Gene Therapy and Biologic Therapy with Interleukin?4
Current Gene Therapy Use of Medication in Coronary Imaging by CT
Current Medical Imaging Angiotensin-Converting Enzyme Inhibitors: Mechanisms of Action and Implications In Anesthesia Practice
Current Pharmaceutical Design Neuroleptic Malignant Syndrome: A Review from a Clinically Oriented Perspective
Current Neuropharmacology Significance of 1,3,4-Oxadiazole Containing Compounds in New Drug Development
Current Drug Research Reviews Toll-Like Receptors and Inflammation in the CNS
Current Drug Targets - Inflammation & Allergy Using Structural and Mechanistic Information to Design Novel Inhibitors/Substrates of P-Glycoprotein
Current Topics in Medicinal Chemistry Pharmacological Properties and Therapeutic Possibilities for Drugs Acting Upon Endocannabinoid Receptors
Current Drug Targets - CNS & Neurological Disorders New Agents to Treat Life-Threatening Fungal Infections
Current Topics in Medicinal Chemistry NTproBNP: An Important Biomarker in Cardiac Diseases
Current Topics in Medicinal Chemistry