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Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide.
Nature 1999; 400(6743):452-7Nat

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, but not the cannabinoid CB1 receptor blocker SR141716A, 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.

Authors+Show Affiliations

Department of Clinical Pharmacology, Institute of Laboratory Medicine, University of Lund, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10440374

Citation

Zygmunt, P M., et al. "Vanilloid Receptors On Sensory Nerves Mediate the Vasodilator Action of Anandamide." Nature, vol. 400, no. 6743, 1999, pp. 452-7.
Zygmunt PM, Petersson J, Andersson DA, et al. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature. 1999;400(6743):452-7.
Zygmunt, P. M., Petersson, J., Andersson, D. A., Chuang, H., Sørgård, M., Di Marzo, V., ... Högestätt, E. D. (1999). Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature, 400(6743), pp. 452-7.
Zygmunt PM, et al. Vanilloid Receptors On Sensory Nerves Mediate the Vasodilator Action of Anandamide. Nature. 1999 Jul 29;400(6743):452-7. PubMed PMID: 10440374.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. AU - Zygmunt,P M, AU - Petersson,J, AU - Andersson,D A, AU - Chuang,H, AU - Sørgård,M, AU - Di Marzo,V, AU - Julius,D, AU - Högestätt,E D, PY - 1999/8/10/pubmed PY - 2001/3/23/medline PY - 1999/8/10/entrez SP - 452 EP - 7 JF - Nature JO - Nature VL - 400 IS - 6743 N2 - 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, but not the cannabinoid CB1 receptor blocker SR141716A, 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. SN - 0028-0836 UR - https://www.unboundmedicine.com/medline/citation/10440374/Vanilloid_receptors_on_sensory_nerves_mediate_the_vasodilator_action_of_anandamide_ L2 - https://doi.org/10.1038/22761 DB - PRIME DP - Unbound Medicine ER -