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Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide

Author

Listed:
  • Peter M. Zygmunt

    (Institute of Laboratory Medicine, University of Lund)

  • Jesper Petersson

    (Institute of Laboratory Medicine, University of Lund)

  • David A. Andersson

    (Institute of Laboratory Medicine, University of Lund)

  • Huai-hu Chuang

    (University of California)

  • Morten Sørgård

    (Institute of Laboratory Medicine, University of Lund)

  • Vincenzo Di Marzo

    (C.N.R. Instituto per la Chimica di Molecole di Interesse Biologico)

  • David Julius

    (University of California)

  • Edward D. Högestätt

    (Institute of Laboratory Medicine, University of Lund)

Abstract

The endogenous cannabinoid receptor agonist anandamide1 is a powerful vasodilator of isolated vascular preparations2,3,4, 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 agonists1 could not mimic the action of anandamide. The selective ‘vanilloid receptor’ antagonist capsazepine6,7 inhibited anandamide-induced vasodilation and release of CGRP. In patch-clamp experiments on cells expressing the cloned vanilloid receptor (VR1)8, 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.

Suggested Citation

  • Peter M. Zygmunt & Jesper Petersson & David A. Andersson & Huai-hu Chuang & Morten Sørgård & Vincenzo Di Marzo & David Julius & Edward D. Högestätt, 1999. "Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide," Nature, Nature, vol. 400(6743), pages 452-457, July.
    • Handle: RePEc:nat:nature:v:400:y:1999:i:6743:d:10.1038_22761
    DOI: 10.1038/22761
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    Cited by:

    1. Burcu Özdemir & Bin Shi & Hans Peter Bantleon & Andreas Moritz & Xiaohui Rausch-Fan & Oleh Andrukhov, 2014. "Endocannabinoids and Inflammatory Response in Periodontal Ligament Cells," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-7, September.
    2. Maxim V Nikolaev & Natalia A Dorofeeva & Margarita S Komarova & Yuliya V Korolkova & Yaroslav A Andreev & Irina V Mosharova & Eugene V Grishin & Denis B Tikhonov & Sergey A Kozlov, 2017. "TRPV1 activation power can switch an action mode for its polypeptide ligands," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-16, May.

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