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CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles

Le, Thi Lisa ; Grell, Anne Sofie LU ; Sheykhzade, Majid ; Warfvinge, Karin LU ; Edvinsson, Lars LU and Sams, Anette (2020) In European Journal of Pharmacology 875.
Abstract

CGRP is a potent dilator of arteries and despite rich perivascular CGRP immunoreactivity in both arteries and veins the role of CGRP in veins remains unknown. The aim of the current study was to compare perivascular CGRP immunoreactivity and expression of CGRP receptor mRNA and CGRP receptor immunoreactivity in rat mesenteric arteries and veins. Furthermore, potential vasomotor effects of CGRP were explored in veins. Immunohistochemical studies reproduced rich perivascular CGRP innervation in arteries and in veins. Further, the presence of mRNA encoding the CGRP receptor subunits, CLR and RAMP1, were demonstrated in both arteries and veins using qPCR. Before comparing the vasoactive effects of CGRP in arteries and veins, we aimed to... (More)

CGRP is a potent dilator of arteries and despite rich perivascular CGRP immunoreactivity in both arteries and veins the role of CGRP in veins remains unknown. The aim of the current study was to compare perivascular CGRP immunoreactivity and expression of CGRP receptor mRNA and CGRP receptor immunoreactivity in rat mesenteric arteries and veins. Furthermore, potential vasomotor effects of CGRP were explored in veins. Immunohistochemical studies reproduced rich perivascular CGRP innervation in arteries and in veins. Further, the presence of mRNA encoding the CGRP receptor subunits, CLR and RAMP1, were demonstrated in both arteries and veins using qPCR. Before comparing the vasoactive effects of CGRP in arteries and veins, we aimed to identify an experimental setting where vasomotor responses could be detected. Therefore, a length-tension study was performed in artery and vein segments. Whereas the arteries showed the characteristic monophasic curve with an IC/IC100 value of 0.9, surprisingly the veins showed a biphasic response with two corresponding IC/IC100 values of 0.7 and 0.9, respectively. There was no significant difference between fresh and cultured vasculature segments. To investigate whether a potential tension-dependent CGRP-induced dilation of veins caused the decline between the two IC/IC100 peaks, a second study was performed, with the CGRP receptor antagonist, BIBN4096BS (olcegepant) and the sensory nerve secretagogue, capsaicin. No significant vascular role of endogenous perivascular CGRP in mesenteric veins could be concluded, and a potential role of the rich perivascular CGRP and CGRP receptor abundancy in veins remains unknown.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Artery, CGRP, Immunohistochemistry, Length-tension, qPCR, Vein
in
European Journal of Pharmacology
volume
875
article number
173033
publisher
Elsevier
external identifiers
  • pmid:32097658
  • scopus:85080955070
ISSN
0014-2999
DOI
10.1016/j.ejphar.2020.173033
language
English
LU publication?
yes
id
05c31b44-b8ad-44f0-8e1e-3a27dd0c300d
date added to LUP
2020-03-17 11:33:29
date last changed
2020-07-08 05:14:08
@article{05c31b44-b8ad-44f0-8e1e-3a27dd0c300d,
  abstract     = {<p>CGRP is a potent dilator of arteries and despite rich perivascular CGRP immunoreactivity in both arteries and veins the role of CGRP in veins remains unknown. The aim of the current study was to compare perivascular CGRP immunoreactivity and expression of CGRP receptor mRNA and CGRP receptor immunoreactivity in rat mesenteric arteries and veins. Furthermore, potential vasomotor effects of CGRP were explored in veins. Immunohistochemical studies reproduced rich perivascular CGRP innervation in arteries and in veins. Further, the presence of mRNA encoding the CGRP receptor subunits, CLR and RAMP1, were demonstrated in both arteries and veins using qPCR. Before comparing the vasoactive effects of CGRP in arteries and veins, we aimed to identify an experimental setting where vasomotor responses could be detected. Therefore, a length-tension study was performed in artery and vein segments. Whereas the arteries showed the characteristic monophasic curve with an IC/IC<sub>100</sub> value of 0.9, surprisingly the veins showed a biphasic response with two corresponding IC/IC<sub>100</sub> values of 0.7 and 0.9, respectively. There was no significant difference between fresh and cultured vasculature segments. To investigate whether a potential tension-dependent CGRP-induced dilation of veins caused the decline between the two IC/IC<sub>100</sub> peaks, a second study was performed, with the CGRP receptor antagonist, BIBN4096BS (olcegepant) and the sensory nerve secretagogue, capsaicin. No significant vascular role of endogenous perivascular CGRP in mesenteric veins could be concluded, and a potential role of the rich perivascular CGRP and CGRP receptor abundancy in veins remains unknown.</p>},
  author       = {Le, Thi Lisa and Grell, Anne Sofie and Sheykhzade, Majid and Warfvinge, Karin and Edvinsson, Lars and Sams, Anette},
  issn         = {0014-2999},
  language     = {eng},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2020.173033},
  doi          = {10.1016/j.ejphar.2020.173033},
  volume       = {875},
  year         = {2020},
}