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Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries

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@article{e9cb4d92c87d4b7a8749697918a4a9da,
title = "Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries",
abstract = "AIM: Calcitonin gene-related peptide (CGRP) and its receptor are widely distributed within the circulation and the mechanism behind its vasodilation not only differs from one animal species to another but is also dependent on the type and size of vessel. The present study examines the nature of CGRP-induced vasodilation, characteristics of the CGRP receptor antagonist telcagepant and localization of the key components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) of the CGRP receptor in human subcutaneous arteries.METHODS: CGRP-induced vasodilation and receptor localization in human subcutaneous arteries were studied by wire myograph in the presence and absence of the CGRP receptor antagonist telcagepant and immunohistochemistry respectively.RESULTS: At concentrations of 1, 3, 5, 10 and 30 nm, telcagepant had a competitive antagonist-like behaviour characterized by a parallel rightwards shift in the log CGRP concentration-tension/calcium curve with no depression of the maximal relaxation. CGRP-induced vasodilation was not affected by mechanical removal of the endothelium or addition of L-NG-nitroarginine methyl ester and indomethacin, antagonists for synthesis of nitric oxide and prostaglandins, respectively. CLR and RAMP1 were localized in the vascular smooth muscle and endothelial cells.CONCLUSION: The present results indicate that CGRP exerts its vasodilatory effect in human subcutaneous arteries by binding to its receptors located on the smooth muscle cells and is suggested to be endothelium-independent. In conclusion, these results underline the dynamic distribution of CGRP receptor components in the human circulation reflecting the important role of CGRP in fine tuning of the blood flow in resistance arteries.",
keywords = "Adult, Aged, Arteries, Azepines, Dinoprost, Dose-Response Relationship, Drug, Endothelium, Vascular, Female, Humans, Imidazoles, Male, Middle Aged, Receptors, Calcitonin Gene-Related Peptide, Subcutaneous Tissue, Young Adult, Journal Article, Research Support, Non-U.S. Gov't",
author = "Lars Edvinsson and H Ahnstedt and R Larsen and M Sheykhzade",
note = "{\textcopyright} 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.",
year = "2014",
month = apr,
doi = "10.1111/apha.12213",
language = "English",
volume = "210",
pages = "811--22",
journal = "Acta Physiologica (Online)",
issn = "1748-1716",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "4",

}

RIS

TY - JOUR

T1 - Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries

AU - Edvinsson, Lars

AU - Ahnstedt, H

AU - Larsen, R

AU - Sheykhzade, M

N1 - © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

PY - 2014/4

Y1 - 2014/4

N2 - AIM: Calcitonin gene-related peptide (CGRP) and its receptor are widely distributed within the circulation and the mechanism behind its vasodilation not only differs from one animal species to another but is also dependent on the type and size of vessel. The present study examines the nature of CGRP-induced vasodilation, characteristics of the CGRP receptor antagonist telcagepant and localization of the key components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) of the CGRP receptor in human subcutaneous arteries.METHODS: CGRP-induced vasodilation and receptor localization in human subcutaneous arteries were studied by wire myograph in the presence and absence of the CGRP receptor antagonist telcagepant and immunohistochemistry respectively.RESULTS: At concentrations of 1, 3, 5, 10 and 30 nm, telcagepant had a competitive antagonist-like behaviour characterized by a parallel rightwards shift in the log CGRP concentration-tension/calcium curve with no depression of the maximal relaxation. CGRP-induced vasodilation was not affected by mechanical removal of the endothelium or addition of L-NG-nitroarginine methyl ester and indomethacin, antagonists for synthesis of nitric oxide and prostaglandins, respectively. CLR and RAMP1 were localized in the vascular smooth muscle and endothelial cells.CONCLUSION: The present results indicate that CGRP exerts its vasodilatory effect in human subcutaneous arteries by binding to its receptors located on the smooth muscle cells and is suggested to be endothelium-independent. In conclusion, these results underline the dynamic distribution of CGRP receptor components in the human circulation reflecting the important role of CGRP in fine tuning of the blood flow in resistance arteries.

AB - AIM: Calcitonin gene-related peptide (CGRP) and its receptor are widely distributed within the circulation and the mechanism behind its vasodilation not only differs from one animal species to another but is also dependent on the type and size of vessel. The present study examines the nature of CGRP-induced vasodilation, characteristics of the CGRP receptor antagonist telcagepant and localization of the key components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) of the CGRP receptor in human subcutaneous arteries.METHODS: CGRP-induced vasodilation and receptor localization in human subcutaneous arteries were studied by wire myograph in the presence and absence of the CGRP receptor antagonist telcagepant and immunohistochemistry respectively.RESULTS: At concentrations of 1, 3, 5, 10 and 30 nm, telcagepant had a competitive antagonist-like behaviour characterized by a parallel rightwards shift in the log CGRP concentration-tension/calcium curve with no depression of the maximal relaxation. CGRP-induced vasodilation was not affected by mechanical removal of the endothelium or addition of L-NG-nitroarginine methyl ester and indomethacin, antagonists for synthesis of nitric oxide and prostaglandins, respectively. CLR and RAMP1 were localized in the vascular smooth muscle and endothelial cells.CONCLUSION: The present results indicate that CGRP exerts its vasodilatory effect in human subcutaneous arteries by binding to its receptors located on the smooth muscle cells and is suggested to be endothelium-independent. In conclusion, these results underline the dynamic distribution of CGRP receptor components in the human circulation reflecting the important role of CGRP in fine tuning of the blood flow in resistance arteries.

KW - Adult

KW - Aged

KW - Arteries

KW - Azepines

KW - Dinoprost

KW - Dose-Response Relationship, Drug

KW - Endothelium, Vascular

KW - Female

KW - Humans

KW - Imidazoles

KW - Male

KW - Middle Aged

KW - Receptors, Calcitonin Gene-Related Peptide

KW - Subcutaneous Tissue

KW - Young Adult

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/apha.12213

DO - 10.1111/apha.12213

M3 - Journal article

C2 - 24330354

VL - 210

SP - 811

EP - 822

JO - Acta Physiologica (Online)

JF - Acta Physiologica (Online)

SN - 1748-1716

IS - 4

ER -

ID: 49203257