Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide

Research output: Contribution to journalLetter

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 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.

Details

Authors
Organisations
External organisations
  • Lund University
  • CNR Istituto per le Tecnologie Applicate ai Beni Culturali (CNR-ITABC)
  • University of California, San Francisco
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology
Original languageEnglish
Pages (from-to)452-457
Number of pages6
JournalNature
Volume400
Issue number6743
Publication statusPublished - 1999 Jul 29
Publication categoryResearch
Peer-reviewedYes