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VIP/PACAP receptors in cerebral arteries of rat: Characterization, localization and relation to intracellular calcium.

Erdling, André LU ; Sheykhzade, Majid; Maddahi, Aida LU ; Bari, Ferenc and Edvinsson, Lars LU (2013) In Neuropeptides 47(2). p.85-92
Abstract
BACKGROUND: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP)-containing nerves surround cerebral blood vessels. The peptides have potent vasodilator properties via smooth muscle cell receptors and activation of adenylate cyclase. The purpose of this study was to describe the effects of two putative VIP/PACAP receptor antagonists and the distribution of the receptor protein in rat brain vessels. METHODS: The vascular effects of VIP, PACAP-27 and PACAP-38 were investigated in segments of rat middle cerebral artery (MCA) by pressurized arteriography, and in a wire myograph. The antagonistic responses to PACAP6-38 and PG99-465 were evaluated. In addition, the receptor subtypes for VIP and PACAP... (More)
BACKGROUND: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP)-containing nerves surround cerebral blood vessels. The peptides have potent vasodilator properties via smooth muscle cell receptors and activation of adenylate cyclase. The purpose of this study was to describe the effects of two putative VIP/PACAP receptor antagonists and the distribution of the receptor protein in rat brain vessels. METHODS: The vascular effects of VIP, PACAP-27 and PACAP-38 were investigated in segments of rat middle cerebral artery (MCA) by pressurized arteriography, and in a wire myograph. The antagonistic responses to PACAP6-38 and PG99-465 were evaluated. In addition, the receptor subtypes for VIP and PACAP (VPAC(1), VPAC(2) and PAC(1)) were visualized in the rat middle cerebral artery by immunohistochemistry and Western blotting. RESULTS: In the perfusion model, abluminal but not luminal VIP, PACAP-27 and PACAP-38 caused concentration-dependent relaxations of the MCA (27.1±0.2%, 25.2±0.4% and 0.3±0.1%, respectively). In the wire myograph, there was no significant difference in potency of the peptides in the MCA. In both systems, PACAP6-38 and PG99-465 inhibited the VIP induced relaxation. Western blot showed the presence of the receptor proteins in cerebral vasculature and immunohistochemistry showed that all three receptors are present and located in the cytoplasm of smooth muscle cells. CONCLUSION: In both systems, the two blockers antagonized the relaxant VIP effect; the potency order of agonists and the immunohistochemistry suggest the presence of the dilatory VPAC(1) and VPAC(2) receptors on the smooth muscle cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neuropeptides
volume
47
issue
2
pages
85 - 92
publisher
Elsevier
external identifiers
  • wos:000316437400004
  • pmid:23375386
  • scopus:84875277038
ISSN
1532-2785
DOI
10.1016/j.npep.2012.12.005
language
English
LU publication?
yes
id
ddf6d3c4-8b58-44e3-8cae-8080184650b8 (old id 3560253)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23375386?dopt=Abstract
date added to LUP
2013-03-01 12:40:59
date last changed
2019-07-16 01:06:20
@article{ddf6d3c4-8b58-44e3-8cae-8080184650b8,
  abstract     = {BACKGROUND: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP)-containing nerves surround cerebral blood vessels. The peptides have potent vasodilator properties via smooth muscle cell receptors and activation of adenylate cyclase. The purpose of this study was to describe the effects of two putative VIP/PACAP receptor antagonists and the distribution of the receptor protein in rat brain vessels. METHODS: The vascular effects of VIP, PACAP-27 and PACAP-38 were investigated in segments of rat middle cerebral artery (MCA) by pressurized arteriography, and in a wire myograph. The antagonistic responses to PACAP6-38 and PG99-465 were evaluated. In addition, the receptor subtypes for VIP and PACAP (VPAC(1), VPAC(2) and PAC(1)) were visualized in the rat middle cerebral artery by immunohistochemistry and Western blotting. RESULTS: In the perfusion model, abluminal but not luminal VIP, PACAP-27 and PACAP-38 caused concentration-dependent relaxations of the MCA (27.1±0.2%, 25.2±0.4% and 0.3±0.1%, respectively). In the wire myograph, there was no significant difference in potency of the peptides in the MCA. In both systems, PACAP6-38 and PG99-465 inhibited the VIP induced relaxation. Western blot showed the presence of the receptor proteins in cerebral vasculature and immunohistochemistry showed that all three receptors are present and located in the cytoplasm of smooth muscle cells. CONCLUSION: In both systems, the two blockers antagonized the relaxant VIP effect; the potency order of agonists and the immunohistochemistry suggest the presence of the dilatory VPAC(1) and VPAC(2) receptors on the smooth muscle cells.},
  author       = {Erdling, André and Sheykhzade, Majid and Maddahi, Aida and Bari, Ferenc and Edvinsson, Lars},
  issn         = {1532-2785},
  language     = {eng},
  number       = {2},
  pages        = {85--92},
  publisher    = {Elsevier},
  series       = {Neuropeptides},
  title        = {VIP/PACAP receptors in cerebral arteries of rat: Characterization, localization and relation to intracellular calcium.},
  url          = {http://dx.doi.org/10.1016/j.npep.2012.12.005},
  volume       = {47},
  year         = {2013},
}