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In-depth characterization of CGRP receptors in human intracranial arteries

Jansen-Olesen, I; Jorgensen, L; Engel, U and Edvinsson, Lars LU (2003) In European Journal of Pharmacology 481(2-3). p.207-216
Abstract
The purpose of the present study was to characterize the effects of human (h) alpha- and beta-calcitonin gene-related peptide (CGRP) on intracranial arteries from man and to investigate the presence of mRNA for the calcitonin receptor like receptor (CRLR) and the receptor activity modifying proteins (RAMPs) 1, 2 and 3, in cerebral and middle meningeal arteries with and without endothelium, in microvessels and in the endothelial cells isolated from the human basilar artery. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of CRLR, RAMP 1, RAMP 2 and RAMP 3 in cerebral and middle meningeal arteries with and without endothelium as well as in microvessels and in the endothelial cells. Human and rat a- and p-CGRP,... (More)
The purpose of the present study was to characterize the effects of human (h) alpha- and beta-calcitonin gene-related peptide (CGRP) on intracranial arteries from man and to investigate the presence of mRNA for the calcitonin receptor like receptor (CRLR) and the receptor activity modifying proteins (RAMPs) 1, 2 and 3, in cerebral and middle meningeal arteries with and without endothelium, in microvessels and in the endothelial cells isolated from the human basilar artery. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of CRLR, RAMP 1, RAMP 2 and RAMP 3 in cerebral and middle meningeal arteries with and without endothelium as well as in microvessels and in the endothelial cells. Human and rat a- and p-CGRP, amylin, adrenomedullin and [acetamidomethyl-Cys(2,7)]human CGRP induced strong concentration-dependent relaxation of human cerebral and middle meningeal arteries. Removal of the endothelium neither changed the maximum relaxant response nor the pIC(50) values for alpha- and beta-CGRP as compared to the responses in arteries with an intact endothelium. Human alpha-CGRP-(8-37) caused a shift of halpha- and hbeta-CGRP-induced relaxations in cerebral and middle meningeal arteries. Calculation of pK(B) values revealed that halpha-CGRP-(8-37) could not significantly discriminate between relaxations induced by halpha-CGRP (pK(B) around 6.8) and hbeta-CGRP (pK(B) around 5.4). There was no significant difference in pK(B) value of halpha-CGRP-(8-37) on hbeta-CGRP-induced relaxation of human cerebral and middle meningeal arteries with and without endothelium. In conclusion, our molecular and pharmacological data support the existence of a single type of CGRP(1) receptors in the human intracranial circulation. (C) 2003 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
human, calcitonin gene-related peptide, vasomotor response, cerebral, artery, meningeal artery
in
European Journal of Pharmacology
volume
481
issue
2-3
pages
207 - 216
publisher
Elsevier
external identifiers
  • wos:000186925400012
  • pmid:14642788
  • scopus:0344827157
ISSN
1879-0712
DOI
language
English
LU publication?
yes
id
372d328a-2e7c-4668-a76e-18aec1d91a1c (old id 293877)
date added to LUP
2007-09-13 12:57:46
date last changed
2018-05-29 11:35:50
@article{372d328a-2e7c-4668-a76e-18aec1d91a1c,
  abstract     = {The purpose of the present study was to characterize the effects of human (h) alpha- and beta-calcitonin gene-related peptide (CGRP) on intracranial arteries from man and to investigate the presence of mRNA for the calcitonin receptor like receptor (CRLR) and the receptor activity modifying proteins (RAMPs) 1, 2 and 3, in cerebral and middle meningeal arteries with and without endothelium, in microvessels and in the endothelial cells isolated from the human basilar artery. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of CRLR, RAMP 1, RAMP 2 and RAMP 3 in cerebral and middle meningeal arteries with and without endothelium as well as in microvessels and in the endothelial cells. Human and rat a- and p-CGRP, amylin, adrenomedullin and [acetamidomethyl-Cys(2,7)]human CGRP induced strong concentration-dependent relaxation of human cerebral and middle meningeal arteries. Removal of the endothelium neither changed the maximum relaxant response nor the pIC(50) values for alpha- and beta-CGRP as compared to the responses in arteries with an intact endothelium. Human alpha-CGRP-(8-37) caused a shift of halpha- and hbeta-CGRP-induced relaxations in cerebral and middle meningeal arteries. Calculation of pK(B) values revealed that halpha-CGRP-(8-37) could not significantly discriminate between relaxations induced by halpha-CGRP (pK(B) around 6.8) and hbeta-CGRP (pK(B) around 5.4). There was no significant difference in pK(B) value of halpha-CGRP-(8-37) on hbeta-CGRP-induced relaxation of human cerebral and middle meningeal arteries with and without endothelium. In conclusion, our molecular and pharmacological data support the existence of a single type of CGRP(1) receptors in the human intracranial circulation. (C) 2003 Elsevier B.V. All rights reserved.},
  author       = {Jansen-Olesen, I and Jorgensen, L and Engel, U and Edvinsson, Lars},
  issn         = {1879-0712},
  keyword      = {human,calcitonin gene-related peptide,vasomotor response,cerebral,artery,meningeal artery},
  language     = {eng},
  number       = {2-3},
  pages        = {207--216},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {In-depth characterization of CGRP receptors in human intracranial arteries},
  url          = {http://dx.doi.org/},
  volume       = {481},
  year         = {2003},
}