Abstract
ATP-sensitive K+ channels, termed KATP channels, provide a link between cellular metabolism and membrane electrical activity in a variety of tissues. Channel isoforms have been identified and are targets for compounds that both stimulate and inhibit their activity resulting in membrane hyperpolarization and depolarization, respectively. Examples include relaxation of vascular smooth muscle and stimulation of insulin secretion. This article reviews the cloning, molecular biology, and structure of KATP channels, with particular focus on the SUR1/KIR6.2 neuroendocrine channels that are important for the regulation of insulin secretion. We integrate the extensive pharmacologic structure-activityrelationship data on these channels, which defines a bipartite drug binding pocket in the SUR (sulfonylurea receptor), with recent structure-function studies that identify domains of SUR and KIR6.2, the channel pore, which are critical for channel assembly, for gating, and for the ligand-receptor interactions that modulate channel activity. The atomic structure of a sulfonylurea in a protein pocket is used to develop insight into the recognition of these compounds. A homology model of KATP channels, based on VC-MsbA, another member of the ABC protein family, is described and used to position amino acids important for the action of channel openers and blockers within the core of SUR. The model has a central chamber which could serve as a multifaceted binding pocket.
Keywords: katp channel, sulfonylurea receptor, inward rectifier, glibenclamide, tolbutamide, repaglinide, potassium channel openers, diazoxide
Current Pharmaceutical Design
Title: Insulin Secretagogues, Sulfonylurea Receptors and KATP Channels
Volume: 11 Issue: 21
Author(s): J. Bryan, A. Crane, W. H. Vila-Carriles, A. P. Babenko and L. Aguilar-Bryan
Affiliation:
Keywords: katp channel, sulfonylurea receptor, inward rectifier, glibenclamide, tolbutamide, repaglinide, potassium channel openers, diazoxide
Abstract: ATP-sensitive K+ channels, termed KATP channels, provide a link between cellular metabolism and membrane electrical activity in a variety of tissues. Channel isoforms have been identified and are targets for compounds that both stimulate and inhibit their activity resulting in membrane hyperpolarization and depolarization, respectively. Examples include relaxation of vascular smooth muscle and stimulation of insulin secretion. This article reviews the cloning, molecular biology, and structure of KATP channels, with particular focus on the SUR1/KIR6.2 neuroendocrine channels that are important for the regulation of insulin secretion. We integrate the extensive pharmacologic structure-activityrelationship data on these channels, which defines a bipartite drug binding pocket in the SUR (sulfonylurea receptor), with recent structure-function studies that identify domains of SUR and KIR6.2, the channel pore, which are critical for channel assembly, for gating, and for the ligand-receptor interactions that modulate channel activity. The atomic structure of a sulfonylurea in a protein pocket is used to develop insight into the recognition of these compounds. A homology model of KATP channels, based on VC-MsbA, another member of the ABC protein family, is described and used to position amino acids important for the action of channel openers and blockers within the core of SUR. The model has a central chamber which could serve as a multifaceted binding pocket.
Export Options
About this article
Cite this article as:
Bryan J., Crane A., Vila-Carriles H. W., Babenko P. A. and Aguilar-Bryan L., Insulin Secretagogues, Sulfonylurea Receptors and KATP Channels, Current Pharmaceutical Design 2005; 11 (21) . https://dx.doi.org/10.2174/1381612054546879
DOI https://dx.doi.org/10.2174/1381612054546879 |
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
?Revolutionizing Cancer Treatment: Nano-Therapeutics Targeting Tumor Microenvironment?
This thematic issue explores the forefront of cancer treatment, centering on the groundbreaking potential of nano-therapeutics meticulously designed to target the tumor microenvironment. At its core, the issue aims to unravel the latest advancements in nanotechnology, showcasing innovative materials, formulations, and delivery systems that hold promise for redefining cancer therapeutics. ...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
- 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
-
Small and Long Non-Coding RNAs: Novel Targets in Perspective Cancer Therapy
Current Genomics Ischemic Post-Conditioning Partially Reverses Cell Cycle Reactivity Following Ischemia/Reperfusion Injury: A Genome-Wide Survey
CNS & Neurological Disorders - Drug Targets Promises and Challenges of MicroRNA-based Treatment of Multiple Myeloma
Current Cancer Drug Targets Tumor Necrosis Factor-α, a Regulator and Therapeutic Agent on Breast Cancer
Current Pharmaceutical Biotechnology Benzo[a]pyrene Toxicity and Inflammatory Disease
Current Rheumatology Reviews Zinc Dependent Histone Deacetylase Inhibitors in Cancer Therapeutics: Recent Update
Current Medicinal Chemistry Docetaxel-loaded Bovine Serum Albumin Nanoparticles Conjugated Docosahexaenoic Acid for Inhibiting Lung Cancer Metastasis to Bone
Anti-Cancer Agents in Medicinal Chemistry The Role of Tumor Suppressor DLC-1: Far From Clear
Anti-Cancer Agents in Medicinal Chemistry Dual Drug Conjugate Loaded Nanoparticles for the Treatment of Cancer
Current Drug Delivery New Potential Serum Biomarkers in Multiple Sclerosis Identified by Proteomic Strategies
Current Medicinal Chemistry Immune Checkpoint Inhibitors in AML-A New Frontier
Current Cancer Drug Targets Insight γ-Secretase: Structure, Function, and Role in Alzheimer’s Disease
Current Drug Targets Lung Cancer and Radiological Imaging
Current Radiopharmaceuticals An Overview on Screening Methods for Lysine Specific Demethylase 1 (LSD1) Inhibitors
Current Medicinal Chemistry New Pharmacological Perspectives and Therapeutic Potential of PPAR-γ Agonists
Current Pharmaceutical Design The SCF-type E3 Ubiquitin Ligases as Cancer Targets
Current Cancer Drug Targets Exploration of Novel Formulations for the Treatment and Diagnosis of Cancer
Nanoscience & Nanotechnology-Asia Radiation Protection of the Child from Diagnostic Imaging
Current Pediatric Reviews Stimuli-Responsive Nanoparticles for siRNA Delivery
Current Pharmaceutical Design Patent Selections:
Recent Patents on Biomedical Engineering (Discontinued)