Abstract
The nicotinic acetylcholine receptor (AChR) is the archetype of the Cys-loop ligand-gated ion channel receptor superfamily. Noncompetitive antagonists inhibit the AChR without interacting directly with agonist sites. Among noncompetitive antagonists, general and local anesthetics have been used for decades to study the structure and function of muscle- as well as neuronal-type AChRs. In this review, we address and update all information regarding the characterization of binding sites and the mechanism of action for n-alkanols, barbiturates, inhalational and dissociative general anesthetics, as well as for tertiary and quaternary local anesthetics. The experimental evidence outlined in this review suggest that: (1) several neuronal-type AChRs might be targets for the pharmacological action of distinct anesthetics; (2) the molecular components of a specific anesthetic locus on a certain receptor type are different from the structural determinants of the site for the same anesthetic on a different receptor type; (3) there are unique binding sites for distinct anesthetics in the same receptor; (4) the affinity of a specific anesthetic depends on the AChR conformational state; (5) anesthetics may inhibit AChRs by different mechanisms including open-channel-blocking, augmenting the desensitization process, and/or inactivating the opening of resting receptors; and (6) some anesthetics may potentiate AChR activity.
Keywords: muscle-type nicotinic acetylcholine receptor, ligand-gated ion channel, transmembrane domain, cytoplasmic domain, cryo-electron microscopy, cys-loop receptor, n-alkanols, barbiturate, dizocilpine, ketamine
Current Protein & Peptide Science
Title: Anesthetics as Chemical Tools to Study the Structure and Function of Nicotinic Acetylcholine Receptors
Volume: 6 Issue: 5
Author(s): Hugo R. Arias and Pankaj Bhumireddy
Affiliation:
Keywords: muscle-type nicotinic acetylcholine receptor, ligand-gated ion channel, transmembrane domain, cytoplasmic domain, cryo-electron microscopy, cys-loop receptor, n-alkanols, barbiturate, dizocilpine, ketamine
Abstract: The nicotinic acetylcholine receptor (AChR) is the archetype of the Cys-loop ligand-gated ion channel receptor superfamily. Noncompetitive antagonists inhibit the AChR without interacting directly with agonist sites. Among noncompetitive antagonists, general and local anesthetics have been used for decades to study the structure and function of muscle- as well as neuronal-type AChRs. In this review, we address and update all information regarding the characterization of binding sites and the mechanism of action for n-alkanols, barbiturates, inhalational and dissociative general anesthetics, as well as for tertiary and quaternary local anesthetics. The experimental evidence outlined in this review suggest that: (1) several neuronal-type AChRs might be targets for the pharmacological action of distinct anesthetics; (2) the molecular components of a specific anesthetic locus on a certain receptor type are different from the structural determinants of the site for the same anesthetic on a different receptor type; (3) there are unique binding sites for distinct anesthetics in the same receptor; (4) the affinity of a specific anesthetic depends on the AChR conformational state; (5) anesthetics may inhibit AChRs by different mechanisms including open-channel-blocking, augmenting the desensitization process, and/or inactivating the opening of resting receptors; and (6) some anesthetics may potentiate AChR activity.
Export Options
About this article
Cite this article as:
Arias R. Hugo and Bhumireddy Pankaj, Anesthetics as Chemical Tools to Study the Structure and Function of Nicotinic Acetylcholine Receptors, Current Protein & Peptide Science 2005; 6 (5) . https://dx.doi.org/10.2174/138920305774329331
DOI https://dx.doi.org/10.2174/138920305774329331 |
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
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
-
Immunotoxins Constructed with Ribosome-Inactivating Proteins and their Enhancers: A Lethal Cocktail with Tumor Specific Efficacy
Current Pharmaceutical Design Meldrum's Acid in Organic Synthesis, an Outlook to Reaction Media
Current Organic Chemistry Subacute Fluoxetine Reduces Signs of Hippocampal Damage Induced by a Single Convulsant Dose of 4-Aminopyridine in Rats
CNS & Neurological Disorders - Drug Targets Molecular Mechanisms, Proteinopathies and Therapeutic Strategies in Neurodegenerative Disorders
Current Genomics Therapeutic Drugs that Slow the Heart Rate of Early Rat Embryos. Is there a Risk for the Human?
Current Pharmaceutical Design Update Clinical Application of Diffusion Tensor Imaging
Current Medical Imaging Evolution of the Human Ion Channel Set
Combinatorial Chemistry & High Throughput Screening Nanotechnology and Drug Delivery: Getting There is Only Half of the Challenge! (Commentary)
CNS & Neurological Disorders - Drug Targets Crosstalk between Inflammation and the BBB in Stroke
Current Neuropharmacology Patient-Specific Induced Pluripotent Stem Cell Models in Mitochondrial Diseases
Current Stem Cell Research & Therapy Editorial [Hot Topic: ABC Transporters in Pharmacology/Physiology and Human Diseases (Guest Editor: Zhe-Sheng (Jason) Chen)]
Current Pharmaceutical Biotechnology ERRATUM 2
Current Neuropharmacology Adult Neurogenesis in Epileptogenesis: An Update for Preclinical Finding and Potential Clinical Translation
Current Neuropharmacology Gene Therapy as a Novel Pharmaceutical Intervention for Stroke
Current Pharmaceutical Design Current κ Opioid Receptor Ligands and Discovery of a New Molecular Scaffold as a κ Opioid Receptor Antagonist Using Pharmacophore-Based Virtual Screening
Current Pharmaceutical Design PET Tracers for Serotonin Receptors and Their Applications
Central Nervous System Agents in Medicinal Chemistry Nanotechnology Driven Approaches for the Management of Parkinson’s Disease: Current Status and Future Perspectives
Current Drug Metabolism New Insights Emerging from Recent Investigations on Human Group II Pyridoxal 5’-Phosphate Decarboxylases
Current Medicinal Chemistry Nitrogen, Oxygen or Sulfur Containing Heterocyclic Compounds as Analgesic Drugs Used as Modulators of the Nitroxidative Stress
Mini-Reviews in Medicinal Chemistry New Perspectives in the Pharmacological Potential of Naringin in Medicine
Current Medicinal Chemistry