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Acta Physiol (Oxf). 2014 Apr;210(4):811-22. doi: 10.1111/apha.12213. Epub 2014 Jan 7.

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

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  • 1Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.

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.

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

KEYWORDS:

MK-0974; affinity; calcitonin gene-related peptide; human subcutaneous artery; telcagepant

PMID:
24330354
[PubMed - indexed for MEDLINE]
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