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Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries.

Edvinsson, Lars LU ; Chan, Kayi Y; Eftekhari, Sajedeh LU ; Nilsson, Elisabeth LU ; de Vries, René; Säveland, Hans LU ; Dirven, Clemens M F; Danser, A H Jan and MaassenVanDenBrink, Antoinette (2010) In Cephalalgia 30(10). p.1233-1240
Abstract
INTRODUCTION: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. MATERIALS AND METHODS: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. We also studied the expression of the CGRP receptor components in cranial arteries with immunocytochemistry. Concentration response curves to αCGRP were performed in human isolated cerebral and middle meningeal arteries in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining. RESULTS: In both... (More)
INTRODUCTION: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. MATERIALS AND METHODS: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. We also studied the expression of the CGRP receptor components in cranial arteries with immunocytochemistry. Concentration response curves to αCGRP were performed in human isolated cerebral and middle meningeal arteries in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining. RESULTS: In both arteries, we found that: (i) telcagepant was devoid of any contractile or relaxant effects per se; (ii) pretreatment with telcagepant antagonised the αCGRP-induced relaxation in a competitive manner; and (iii) immunohistochemistry revealed expression and co-localisation of CLR and RAMP1 in the smooth muscle cells in the media layer of both arteries. CONCLUSIONS: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral and meningeal arteries, which illustrates a possible site of action of telcagepant in the treatment of migraine. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cephalalgia
volume
30
issue
10
pages
1233 - 1240
publisher
Wiley-Blackwell
external identifiers
  • WOS:000285052900011
  • PMID:20855369
  • Scopus:79952113515
ISSN
0333-1024
DOI
10.1177/0333102410362122
language
English
LU publication?
yes
id
ccea4d89-3066-4314-83ec-43918d6ebd23 (old id 1688048)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20855369?dopt=Abstract
date added to LUP
2010-10-05 10:37:04
date last changed
2016-10-13 04:31:40
@misc{ccea4d89-3066-4314-83ec-43918d6ebd23,
  abstract     = {INTRODUCTION: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. MATERIALS AND METHODS: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. We also studied the expression of the CGRP receptor components in cranial arteries with immunocytochemistry. Concentration response curves to αCGRP were performed in human isolated cerebral and middle meningeal arteries in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining. RESULTS: In both arteries, we found that: (i) telcagepant was devoid of any contractile or relaxant effects per se; (ii) pretreatment with telcagepant antagonised the αCGRP-induced relaxation in a competitive manner; and (iii) immunohistochemistry revealed expression and co-localisation of CLR and RAMP1 in the smooth muscle cells in the media layer of both arteries. CONCLUSIONS: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral and meningeal arteries, which illustrates a possible site of action of telcagepant in the treatment of migraine.},
  author       = {Edvinsson, Lars and Chan, Kayi Y and Eftekhari, Sajedeh and Nilsson, Elisabeth and de Vries, René and Säveland, Hans and Dirven, Clemens M F and Danser, A H Jan and MaassenVanDenBrink, Antoinette},
  issn         = {0333-1024},
  language     = {eng},
  number       = {10},
  pages        = {1233--1240},
  publisher    = {ARRAY(0xb700280)},
  series       = {Cephalalgia},
  title        = {Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries.},
  url          = {http://dx.doi.org/10.1177/0333102410362122},
  volume       = {30},
  year         = {2010},
}