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.
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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 |
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