Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide

Peter M. Zygmunt, Jesper Petersson, David A. Andersson, Huai-hu Chuang, Morten Sørgård, Vincenzo Di Marzo, David Julius and Edward D. Högestätt ()
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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

Nature, 1999, vol. 400, issue 6743, 452-457

Abstract: 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.

Date: 1999
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DOI: 10.1038/22761

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