Abstract
Calcitonin gene related peptide (CGRP) is a vasodilator. Its plasma levels are altered in several human diseases, including migraine, hypertension and diabetes. CGRP is locally released by motor neurons, and is overexpressed in response to surgical or pharmacological blockage of neuromuscular transmission. Additionally to a brief discussion with regard to the clinical relevance of CGRP, this review focuses on the effects of CGRP on skeletal muscle excitation-contraction (EC) coupling, as well as the corresponding pathohysiological consequences. EC coupling involves activation of 2 different types of calcium channels: dihydropyridine receptors (DHPRs) located at the sarcolemma, and ryanodine receptors (RyR1s) located at the sarcoplasmic reticulum (SR). In response to electrical depolarization, DHPRs activate nearby and physically bound RyR1s, allowing Ca2+ from the SR to move into the cytosol (termed voltage-gated Ca2+ release, or VGCR). We recently found that CGRP stimulates VGCR by 350 % in as short as 1h. This effect, which lasts for at least 48 h, is due to activation of the CGRP receptor, and requires activation of the cAMP/PKA signaling pathway. CGRP also increases the amplitude of caffeine-induced Ca2+ release (400 %); suggesting increased SR Ca2+ content underlies stimulation of VGCR. Interestingly, in the long-term CGRP also increases the density of sarcolemmal DHPRs (up to 30%, within 24-48 h). We propose that these CGRP effects may contribute to prevent and/or restore symptoms in central core disease (CCD); a congenital myopathy that is linked to mutations in the gene encoding RyR1.
Keywords: Calcitonin-gene-related peptide, excitation-contraction coupling, calcium channels, neuromuscular junction, central core disease, dihydropyridine receptor, ryanodine receptor, intracellular calcium
Current Vascular Pharmacology
Title: CGRP, a Vasodilator Neuropeptide that Stimulates Neuromuscular Transmission and EC Coupling
Volume: 8 Issue: 3
Author(s): Ana Victoria Vega and Guillermo Avila
Affiliation:
Keywords: Calcitonin-gene-related peptide, excitation-contraction coupling, calcium channels, neuromuscular junction, central core disease, dihydropyridine receptor, ryanodine receptor, intracellular calcium
Abstract: Calcitonin gene related peptide (CGRP) is a vasodilator. Its plasma levels are altered in several human diseases, including migraine, hypertension and diabetes. CGRP is locally released by motor neurons, and is overexpressed in response to surgical or pharmacological blockage of neuromuscular transmission. Additionally to a brief discussion with regard to the clinical relevance of CGRP, this review focuses on the effects of CGRP on skeletal muscle excitation-contraction (EC) coupling, as well as the corresponding pathohysiological consequences. EC coupling involves activation of 2 different types of calcium channels: dihydropyridine receptors (DHPRs) located at the sarcolemma, and ryanodine receptors (RyR1s) located at the sarcoplasmic reticulum (SR). In response to electrical depolarization, DHPRs activate nearby and physically bound RyR1s, allowing Ca2+ from the SR to move into the cytosol (termed voltage-gated Ca2+ release, or VGCR). We recently found that CGRP stimulates VGCR by 350 % in as short as 1h. This effect, which lasts for at least 48 h, is due to activation of the CGRP receptor, and requires activation of the cAMP/PKA signaling pathway. CGRP also increases the amplitude of caffeine-induced Ca2+ release (400 %); suggesting increased SR Ca2+ content underlies stimulation of VGCR. Interestingly, in the long-term CGRP also increases the density of sarcolemmal DHPRs (up to 30%, within 24-48 h). We propose that these CGRP effects may contribute to prevent and/or restore symptoms in central core disease (CCD); a congenital myopathy that is linked to mutations in the gene encoding RyR1.
Export Options
About this article
Cite this article as:
Victoria Vega Ana and Avila Guillermo, CGRP, a Vasodilator Neuropeptide that Stimulates Neuromuscular Transmission and EC Coupling, Current Vascular Pharmacology 2010; 8 (3) . https://dx.doi.org/10.2174/157016110791112287
DOI https://dx.doi.org/10.2174/157016110791112287 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
Advancements in Arterial Stiffness: Novel Therapeutic Frontiers
Arterial stiffness, a hallmark of cardiovascular disease, poses significant challenges in contemporary healthcare. This thematic issue delves into the multifaceted landscape of arterial stiffness and explores cutting-edge therapeutic interventions aimed at mitigating its adverse effects. Within these pages, readers will find a comprehensive overview of the mechanisms underlying arterial stiffness, ...read more
Ischemic Cardiovascular Diseases: Mechanisms, Diagnosis and Therapy
Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...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
-
Addiction Liability of Pharmacotherapeutic Interventions in Obesity
Current Pharmaceutical Design B-Type Natriuretic Peptide for Diagnosis and Therapy
Recent Patents on Cardiovascular Drug Discovery Aldosteronism in Heart Failure: A Proinflammatory / Fibrogenic Cardiac Phenotype. Search for Biomarkers and Potential Drug Targets
Current Drug Targets Molecular Pathophysiology of Renal Tubular Acidosis
Current Genomics Relaxin as a Cardiovascular Hormone: Physiology, Pathophysiology and Therapeutic Promises
Cardiovascular & Hematological Agents in Medicinal Chemistry Vaccination Against High Blood Pressure
Current Pharmaceutical Design Advance in Understanding the Biosynthesis of Prostacyclin and Thromboxane A2 in the Endoplasmic Reticulum Membrane via the Cyclooxygenase Pathway
Mini-Reviews in Medicinal Chemistry Cystatin C: An Emerging Biomarker in Cardiovascular Disease
Current Topics in Medicinal Chemistry Merging Transport Data for Choroid Plexus with Blood-Brain Barrier to Model CNS Homeostasis and Disease More Effectively
CNS & Neurological Disorders - Drug Targets Therapeutic Potential of Erythropoietin in Retinal and Optic Nerve Diseases
CNS & Neurological Disorders - Drug Targets Chemotherapeutic Options for Colorectal Cancer Patients with Cardiovascular Diseases.
Reviews on Recent Clinical Trials Capillary Degeneration and Right Ventricular Remodeling Due to Hypoxic Stress with Sugen5416
Current Vascular Pharmacology A Review of Selected Adult Congenital Heart Diseases Encountered in Daily Practice
Current Cardiology Reviews Are Calcium Channel Blockers First-Line Drugs for the Treatment of Hypertension and Cardiovascular Disease?
Current Hypertension Reviews The Economics of Pharmacogenomics
Current Pharmacogenomics New Organ-Specific Drug Strategies Interfering in Signaling Pathways: Kinase Inhibitors and Other New Developmental Drugs in HCC
Current Signal Transduction Therapy Amplified Crosstalk Between Estrogen Binding and GFR Signaling Mediated Pathways of ER Activation Drives Responses in Tumors Treated with Endocrine Disruptors
Recent Patents on Anti-Cancer Drug Discovery The Cannabinoids Switch of Oxidative Stress: A Double-Edged Sword
Mini-Reviews in Organic Chemistry Nitric Oxide and L-Arginine Deficiency in Cystic Fibrosis
Current Pharmaceutical Design A Case of Ischemic Stroke in Acute Promyelocytic Leukemia at Initial Presentation: Relevance of All-Trans Retinoic Acid Treatment
Cardiovascular & Hematological Disorders-Drug Targets