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Immunohistochemical localization of calcitonin receptor-like receptor and receptor activity-modifying proteins in the human cerebral vasculature

Oliver, K R; Wainwright, A; Edvinsson, Lars LU ; Pickard, J D and Hill, R G (2002) In Journal of Cerebral Blood Flow and Metabolism 22(5). p.620-629
Abstract
Calcitonin gene-related peptide and adrenomedullin belong to a structurally related neuropeptide family and are potent vasodilators expressed in the trigeminovascular system. The molecular identity of receptors for these proteins has only recently been elucidated. Central to functional binding of these neuropeptides is the G-protein-coupled receptor, the calcitonin receptor-like receptor (CRLR), Whose cell surface expression and pharmacology is determined by coexpression of a receptor activity-modifying protein (RAMP). CRLR combined with RAMP1 binds calcitonin gene-related peptide With high affinity. whereas CRLR coexpression with RAMP2 or -3 confers, high-affinity binding of adrenomedullin. The authors investigated the expression of these... (More)
Calcitonin gene-related peptide and adrenomedullin belong to a structurally related neuropeptide family and are potent vasodilators expressed in the trigeminovascular system. The molecular identity of receptors for these proteins has only recently been elucidated. Central to functional binding of these neuropeptides is the G-protein-coupled receptor, the calcitonin receptor-like receptor (CRLR), Whose cell surface expression and pharmacology is determined by coexpression of a receptor activity-modifying protein (RAMP). CRLR combined with RAMP1 binds calcitonin gene-related peptide With high affinity. whereas CRLR coexpression with RAMP2 or -3 confers, high-affinity binding of adrenomedullin. The authors investigated the expression of these receptor components in human cerebral vasculature to further characterize neuropeptide receptor content and the potential functions of these receptors. Localization has been carried out using specific antisera raised against immunogenic peptide sequences that were subsequently applied using modern immunohistochemical techniques and confocal microscopy. The results are the first to show the presence of these receptor component proteins in human middle meningeal, middle cerebral. pial, and superficial temporal vessels, and confirm that both calcitonin gene-related peptide and adrenomedullin receptors may arise from the coassembly of RAMPs with CRLR in these vessel type,,. These novel data advance the understanding of the molecular function of the trigeminovascular system, its potential role in vascular headache disorders such as migraine. and may lead to possible Ways in which future synthetic ligands may be applied to manage these disorders. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
immunohistochemistry, trigeminovascular system, peptide receptors
in
Journal of Cerebral Blood Flow and Metabolism
volume
22
issue
5
pages
620 - 629
publisher
Nature Publishing Group
external identifiers
  • wos:000175371200014
  • pmid:11973435
  • scopus:0036253810
ISSN
1559-7016
DOI
10.1097/00004647-200205000-00014
language
English
LU publication?
yes
id
3823c8f0-fa1f-4c0a-bbbc-67d5974e14cc (old id 338602)
date added to LUP
2007-11-02 13:55:23
date last changed
2017-10-22 04:42:00
@article{3823c8f0-fa1f-4c0a-bbbc-67d5974e14cc,
  abstract     = {Calcitonin gene-related peptide and adrenomedullin belong to a structurally related neuropeptide family and are potent vasodilators expressed in the trigeminovascular system. The molecular identity of receptors for these proteins has only recently been elucidated. Central to functional binding of these neuropeptides is the G-protein-coupled receptor, the calcitonin receptor-like receptor (CRLR), Whose cell surface expression and pharmacology is determined by coexpression of a receptor activity-modifying protein (RAMP). CRLR combined with RAMP1 binds calcitonin gene-related peptide With high affinity. whereas CRLR coexpression with RAMP2 or -3 confers, high-affinity binding of adrenomedullin. The authors investigated the expression of these receptor components in human cerebral vasculature to further characterize neuropeptide receptor content and the potential functions of these receptors. Localization has been carried out using specific antisera raised against immunogenic peptide sequences that were subsequently applied using modern immunohistochemical techniques and confocal microscopy. The results are the first to show the presence of these receptor component proteins in human middle meningeal, middle cerebral. pial, and superficial temporal vessels, and confirm that both calcitonin gene-related peptide and adrenomedullin receptors may arise from the coassembly of RAMPs with CRLR in these vessel type,,. These novel data advance the understanding of the molecular function of the trigeminovascular system, its potential role in vascular headache disorders such as migraine. and may lead to possible Ways in which future synthetic ligands may be applied to manage these disorders.},
  author       = {Oliver, K R and Wainwright, A and Edvinsson, Lars and Pickard, J D and Hill, R G},
  issn         = {1559-7016},
  keyword      = {immunohistochemistry,trigeminovascular system,peptide receptors},
  language     = {eng},
  number       = {5},
  pages        = {620--629},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Cerebral Blood Flow and Metabolism},
  title        = {Immunohistochemical localization of calcitonin receptor-like receptor and receptor activity-modifying proteins in the human cerebral vasculature},
  url          = {http://dx.doi.org/10.1097/00004647-200205000-00014},
  volume       = {22},
  year         = {2002},
}