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Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide

Zygmunt, Peter M. LU orcid ; Petersson, Jesper LU ; Andersson, David A. LU ; Chuang, Huai Hu ; Sørgård, Morten ; Di Marzo, Vincenzo ; Julius, David and Högestätt, Edward D. LU (1999) In Nature 400(6743). p.452-457
Abstract

The endogenous cannabinoid receptor agonist anandamide is a powerful vasodilator of isolated vascular preparations, but its mechanism of action is unclear. Here we show that the vasodilator response to anandamide in isolated arteries is capsaicin-sensitive and accompanied by release of calcitonin- gene-related peptide (CGRP). The selective CGRP-receptor antagonist 8-37 CGRP (ref. 5), but not the cannabinoid CB1 receptor blocker SR141716A (ref. 7), inhibited the vasodilator effect of anandamide. Other endogenous. (2- arachidonylglycerol, palmitylethanolamide) and synthetic (HU 210, WIN 55,212- 2, CP 55,940) CB1 and CB2 receptor agonists could not mimic the action of anandamide. The selective 'vanilloid receptor' antagonist capsazepine... (More)

The endogenous cannabinoid receptor agonist anandamide is a powerful vasodilator of isolated vascular preparations, but its mechanism of action is unclear. Here we show that the vasodilator response to anandamide in isolated arteries is capsaicin-sensitive and accompanied by release of calcitonin- gene-related peptide (CGRP). The selective CGRP-receptor antagonist 8-37 CGRP (ref. 5), but not the cannabinoid CB1 receptor blocker SR141716A (ref. 7), inhibited the vasodilator effect of anandamide. Other endogenous. (2- arachidonylglycerol, palmitylethanolamide) and synthetic (HU 210, WIN 55,212- 2, CP 55,940) CB1 and CB2 receptor agonists could not mimic the action of anandamide. The selective 'vanilloid receptor' antagonist capsazepine inhibited anandamide-induced vasodilation and release of CGRP. In patch-clamp experiments on cells expressing the cloned vanilloid receptor (VR1), anandamide induced a capsazepine-sensitive current in whole cells and isolated membrane patches. Our results indicate that anandamide induces vasodilation by activating vanilloid receptors on perivascular sensory nerves and causing release of CGRP. The vanilloid receptor may thus be another molecular target for endogenous anandamide, besides cannabinoid receptors, in the nervous and cardiovascular systems.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature
volume
400
issue
6743
pages
6 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:0033614984
  • pmid:10440374
ISSN
0028-0836
DOI
10.1038/22761
language
English
LU publication?
yes
id
9e9cb0ea-d35d-4ec3-b558-56cf74f9fd3f
date added to LUP
2019-05-31 21:37:02
date last changed
2024-06-26 19:35:42
@article{9e9cb0ea-d35d-4ec3-b558-56cf74f9fd3f,
  abstract     = {{<p>The endogenous cannabinoid receptor agonist anandamide is a powerful vasodilator of isolated vascular preparations, but its mechanism of action is unclear. Here we show that the vasodilator response to anandamide in isolated arteries is capsaicin-sensitive and accompanied by release of calcitonin- gene-related peptide (CGRP). The selective CGRP-receptor antagonist 8-37 CGRP (ref. 5), but not the cannabinoid CB1 receptor blocker SR141716A (ref. 7), inhibited the vasodilator effect of anandamide. Other endogenous. (2- arachidonylglycerol, palmitylethanolamide) and synthetic (HU 210, WIN 55,212- 2, CP 55,940) CB1 and CB2 receptor agonists could not mimic the action of anandamide. The selective 'vanilloid receptor' antagonist capsazepine inhibited anandamide-induced vasodilation and release of CGRP. In patch-clamp experiments on cells expressing the cloned vanilloid receptor (VR1), anandamide induced a capsazepine-sensitive current in whole cells and isolated membrane patches. Our results indicate that anandamide induces vasodilation by activating vanilloid receptors on perivascular sensory nerves and causing release of CGRP. The vanilloid receptor may thus be another molecular target for endogenous anandamide, besides cannabinoid receptors, in the nervous and cardiovascular systems.</p>}},
  author       = {{Zygmunt, Peter M. and Petersson, Jesper and Andersson, David A. and Chuang, Huai Hu and Sørgård, Morten and Di Marzo, Vincenzo and Julius, David and Högestätt, Edward D.}},
  issn         = {{0028-0836}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{6743}},
  pages        = {{452--457}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature}},
  title        = {{Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide}},
  url          = {{http://dx.doi.org/10.1038/22761}},
  doi          = {{10.1038/22761}},
  volume       = {{400}},
  year         = {{1999}},
}