Abstract
Release of acetylcholine from parasympathetic nerves in the airways activates postjunctional muscarinic receptors present on smooth muscle, submucosal glands and blood vessels. This triggers bronchoconstriction, muscle hypertrophy, mucus secretion, and vasodilatation, respectively. The release of acetylcholine from parasympathetic nerves in lungs is induced by a variety of stimuli and downregulated by the inhibitory activity of neuronal M2 muscarinic receptors via a feedback mechanism. Increased parasympathetic nerve activity occurs in a variety of airway diseases in childhood, including viral-induced wheeze and asthma. Common to these conditions are reversible airway obstruction, mucus hypersecretion, vasodilation and enhanced vascular permeability. In animal models of airway hyperreactivity similar findings of increased acetylcholine release resulting in enhanced supply of this neurotransmitter to the postjunctional smooth muscles, submucosal glands and airway vessels, were demonstrated. While the number and function of postjunctional muscarinic receptors in the airways are unchanged in such airway disorders, inhibitory activity on the parasympathetic nerves appears to be impaired. Specifically, M2 muscarinic receptor dysfunction has been demonstrated in models of bronchial hyperreactivity induced by a variety of triggers, including viruses, atmospheric pollutants and allergens. The mechanisms leading to impairment of neuronal M2 muscarinic receptor function and their putative relevance to the pathogenesis and the treatment of airway disease in childhood are described. Finally, the available data on the activity of ipratropium bromide, a short-acting anticholinergic drug, in the most common pediatric airway disease are reported and the possible therapeutic efficacy of tiotropium bromide, a more recently introduced long-acting, selective anticholinergic compound, is discussed.
Keywords: Acetylcholine, muscarinic receptors, bronchiolitis, pre-school wheezing, asthma, cystic fibrosis, chronic lung disease of prematurity, airway obstruction, viruses, allergens
Current Pharmaceutical Design
Title:Treatment of Disorders Characterized by Reversible Airway Obstruction in Childhood: are Anti-cholinergic Agents the Answer?
Volume: 18 Issue: 21
Author(s): Annabelle Quizon, Andrew A. Colin, Umberto Pelosi and Giovanni A. Rossi
Affiliation:
Keywords: Acetylcholine, muscarinic receptors, bronchiolitis, pre-school wheezing, asthma, cystic fibrosis, chronic lung disease of prematurity, airway obstruction, viruses, allergens
Abstract: Release of acetylcholine from parasympathetic nerves in the airways activates postjunctional muscarinic receptors present on smooth muscle, submucosal glands and blood vessels. This triggers bronchoconstriction, muscle hypertrophy, mucus secretion, and vasodilatation, respectively. The release of acetylcholine from parasympathetic nerves in lungs is induced by a variety of stimuli and downregulated by the inhibitory activity of neuronal M2 muscarinic receptors via a feedback mechanism. Increased parasympathetic nerve activity occurs in a variety of airway diseases in childhood, including viral-induced wheeze and asthma. Common to these conditions are reversible airway obstruction, mucus hypersecretion, vasodilation and enhanced vascular permeability. In animal models of airway hyperreactivity similar findings of increased acetylcholine release resulting in enhanced supply of this neurotransmitter to the postjunctional smooth muscles, submucosal glands and airway vessels, were demonstrated. While the number and function of postjunctional muscarinic receptors in the airways are unchanged in such airway disorders, inhibitory activity on the parasympathetic nerves appears to be impaired. Specifically, M2 muscarinic receptor dysfunction has been demonstrated in models of bronchial hyperreactivity induced by a variety of triggers, including viruses, atmospheric pollutants and allergens. The mechanisms leading to impairment of neuronal M2 muscarinic receptor function and their putative relevance to the pathogenesis and the treatment of airway disease in childhood are described. Finally, the available data on the activity of ipratropium bromide, a short-acting anticholinergic drug, in the most common pediatric airway disease are reported and the possible therapeutic efficacy of tiotropium bromide, a more recently introduced long-acting, selective anticholinergic compound, is discussed.
Export Options
About this article
Cite this article as:
Quizon Annabelle, A. Colin Andrew, Pelosi Umberto and A. Rossi Giovanni, Treatment of Disorders Characterized by Reversible Airway Obstruction in Childhood: are Anti-cholinergic Agents the Answer?, Current Pharmaceutical Design 2012; 18 (21) . https://dx.doi.org/10.2174/1381612811209023061
DOI https://dx.doi.org/10.2174/1381612811209023061 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Recent Advances in Fe-MOF Compositions for Biomedical Applications
Current Medicinal Chemistry Selective Inhibitors of Inducible Nitric Oxide Synthase: Potential Agents for the Treatment of Inflammatory Diseases?
Current Topics in Medicinal Chemistry The Effect of Lead Exposure on Selected Blood Inflammatory Biomarkers in Guinea pigs
Cardiovascular & Hematological Disorders-Drug Targets Foam Preparations for the Treatment of Ulcerative Colitis
Current Drug Delivery Occupational Exposure and Occupational Asthma: Difference in Practices in Developed Countries v/s Developing Countries
Current Respiratory Medicine Reviews Local Renin-Angiotensin II Systems, Angiotensin-Converting Enzyme and its Homologue ACE2: Their Potential Role in the Pathogenesis of Chronic Obstructive Pulmonary Diseases, Pulmonary Hypertension and Acute Respiratory Distress Syndrome
Current Medicinal Chemistry The Role of Lymphocytes in the Pathogenesis of Asthma and COPD
Current Medicinal Chemistry The Possibilities and Pitfalls for Anti-Complement Therapies in Inflammatory Diseases
Current Drug Targets - Inflammation & Allergy 3D-QSAR of Novel Phosphodiesterase-4 Inhibitors by Genetic Function Approximation
Medicinal Chemistry Morbidity and Mortality Associated with Pharmacotherapy. Evolution and Current Concept of Drug-Related Problems
Current Pharmaceutical Design Growth Restriction: Etiology, Maternal and Neonatal Outcome. A Review
Current Women`s Health Reviews A Focus on Pharmacological Management of Catecholaminergic Polymorphic Ventricular Tachycardia
Mini-Reviews in Medicinal Chemistry Emerging Role of NF-κB in the Pathogenesis of Hepatic Encephalopathy
Current Signal Transduction Therapy Integration of Virtual and High Throughput Screening in Lead Discovery Settings
Combinatorial Chemistry & High Throughput Screening Prevalence, Presentation and Outcome of Secondary Bloodstream Infections among COVID-19 Patients
Infectious Disorders - Drug Targets Inflammasome in Dendritic Cells Immunobiology: Implications to Diseases and Therapeutic Strategies
Current Drug Targets Immunologic Diseases and Brain Tumors
Inflammation & Allergy - Drug Targets (Discontinued) Histone Deacetylase Inhibitors: New Promise in the Treatment of Immune and Inflammatory Diseases
Current Drug Targets Prevalence and Factors Associated With Low Aerobic Performance Levels in Adolescents: A Systematic Review
Current Pediatric Reviews IL-37 As a Potential Biotherapeutics of Inflammatory Diseases
Current Drug Targets