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Pharmacological characterization and expression of VIP and PACAP receptors in isolated cranial arteries of the rat

Baun, Michael; Hay-Schmidt, Anders; Edvinsson, Lars LU ; Olesen, Jes and Jansen-Olesen, Inger (2011) In European Journal of Pharmacology 670(1). p.186-194
Abstract
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) are potent vasodilators in animals and humans. PACAP infusion but not VIP infusion precipitates migraine attacks in migraine patients. The vascular effects of VIP and the two varieties of PACAP (PACAP-27 and PACAP-38) were investigated versus selective antagonists in segments of rat middle cerebral arteries (MCA), basilar arteries (BA) and middle meningeal arteries (MMA) using myographs. The luminal and abluminal effects of VIP were studied using perfusion myograph. mRNA expression of the relevant receptors (VPAC(1), VPAC(2) and PAC(1)) was examined by in situ hybridization. There was no significant difference in relaxant potency of the peptides... (More)
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) are potent vasodilators in animals and humans. PACAP infusion but not VIP infusion precipitates migraine attacks in migraine patients. The vascular effects of VIP and the two varieties of PACAP (PACAP-27 and PACAP-38) were investigated versus selective antagonists in segments of rat middle cerebral arteries (MCA), basilar arteries (BA) and middle meningeal arteries (MMA) using myographs. The luminal and abluminal effects of VIP were studied using perfusion myograph. mRNA expression of the relevant receptors (VPAC(1), VPAC(2) and PAC(1)) was examined by in situ hybridization. There was no significant difference in relaxant potency of the peptides in the MCA. In BA the relaxant potency was VIP>PACAP-27 = PACAP-38. Relaxant responses were either absent or very weak in MMA. VIP was found to be somewhat more potent in BA than in the MCA. Maxadilan, a selective PAC(1)-receptor agonist, showed no relaxant effect in either vessel. The VPAC(2)-antagonist PG 99-465 alone proved ineffective in the MCA, while it had a weak effect on BA. The VPAC(1)-antagonist PG 97269 inhibited relaxation induced by both VIP and the PACAPs in cerebral vessels. In combination, the two antagonists demonstrated better effect than either alone. VIP applied luminally via perfusion myograph caused no dilatation, indicating lack of endothelial involvement. In situ hybridization demonstrated the presence of mRNA for all three receptors in the smooth muscle cells of the vessels. In conclusion, migraine-like headache induced by PACAP-38 infusion is unlikely to be caused by direct vasodilator action on intracranial vessels. (C) 2011 Elsevier B.V. All rights reserved. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
PACAP, VIP, Myograph, Perfusion myograph, In situ hybridization, Migraine, Neuropeptide, VPAC(1), VPAC(2), PAC(1)
in
European Journal of Pharmacology
volume
670
issue
1
pages
186 - 194
publisher
Elsevier
external identifiers
  • wos:000296550500026
  • scopus:80054735800
ISSN
1879-0712
DOI
10.1016/j.ejphar.2011.08.016
language
English
LU publication?
yes
id
f510065a-1090-4aeb-ade9-699e5394ae22 (old id 2254479)
date added to LUP
2012-01-02 08:06:50
date last changed
2017-08-27 03:35:08
@article{f510065a-1090-4aeb-ade9-699e5394ae22,
  abstract     = {Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) are potent vasodilators in animals and humans. PACAP infusion but not VIP infusion precipitates migraine attacks in migraine patients. The vascular effects of VIP and the two varieties of PACAP (PACAP-27 and PACAP-38) were investigated versus selective antagonists in segments of rat middle cerebral arteries (MCA), basilar arteries (BA) and middle meningeal arteries (MMA) using myographs. The luminal and abluminal effects of VIP were studied using perfusion myograph. mRNA expression of the relevant receptors (VPAC(1), VPAC(2) and PAC(1)) was examined by in situ hybridization. There was no significant difference in relaxant potency of the peptides in the MCA. In BA the relaxant potency was VIP>PACAP-27 = PACAP-38. Relaxant responses were either absent or very weak in MMA. VIP was found to be somewhat more potent in BA than in the MCA. Maxadilan, a selective PAC(1)-receptor agonist, showed no relaxant effect in either vessel. The VPAC(2)-antagonist PG 99-465 alone proved ineffective in the MCA, while it had a weak effect on BA. The VPAC(1)-antagonist PG 97269 inhibited relaxation induced by both VIP and the PACAPs in cerebral vessels. In combination, the two antagonists demonstrated better effect than either alone. VIP applied luminally via perfusion myograph caused no dilatation, indicating lack of endothelial involvement. In situ hybridization demonstrated the presence of mRNA for all three receptors in the smooth muscle cells of the vessels. In conclusion, migraine-like headache induced by PACAP-38 infusion is unlikely to be caused by direct vasodilator action on intracranial vessels. (C) 2011 Elsevier B.V. All rights reserved.},
  author       = {Baun, Michael and Hay-Schmidt, Anders and Edvinsson, Lars and Olesen, Jes and Jansen-Olesen, Inger},
  issn         = {1879-0712},
  keyword      = {PACAP,VIP,Myograph,Perfusion myograph,In situ hybridization,Migraine,Neuropeptide,VPAC(1),VPAC(2),PAC(1)},
  language     = {eng},
  number       = {1},
  pages        = {186--194},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Pharmacological characterization and expression of VIP and PACAP receptors in isolated cranial arteries of the rat},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2011.08.016},
  volume       = {670},
  year         = {2011},
}