Journal ArticleDOI
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
Peter M. Zygmunt,Jesper Petersson,David Andersson,Huai-hu Chuang,Morten Sørgård,Vincenzo Di Marzo,David Julius,Edward D. Högestätt +7 more
Reads0
Chats0
TLDR
It is shown that the vasodilator response to anandamide in isolated arteries is capsaicin-sensitive and accompanied by release of calcitonin-gene-related peptide (CGRP), which indicates that the vanilloid receptor may be another molecular target for endogenousAnandamide, besides cannabinoid receptors, in the nervous and cardiovascular systems.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.read more
Citations
More filters
Journal ArticleDOI
Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor
Michael J. Caterina,A. Leffler,Annika B. Malmberg,William J. Martin,Jodie A. Trafton,K. R. Petersen-Zeitz,Martin Koltzenburg,Allan I. Basbaum,David Julius +8 more
TL;DR: Sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli and are impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation.
Journal ArticleDOI
International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors
Allyn C. Howlett,Francis Barth,Tom I. Bonner,Guy A. Cabral,Pierre Casellas,William A. Devane,Christian C. Felder,Miles Herkenham,Ken Mackie,Billy R. Martin,Raphael Mechoulam,Roger G. Pertwee +11 more
TL;DR: It is considered premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification, because pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging and other kinds of supporting evidence are still lacking.
Journal ArticleDOI
Molecular mechanisms of nociception
David Julius,Allan I. Basbaum +1 more
TL;DR: Efforts to determine how primary sensory neurons detect pain-producing stimuli of a thermal, mechanical or chemical nature have revealed new signalling mechanisms and brought us closer to understanding the molecular events that facilitate transitions from acute to persistent pain.
Journal ArticleDOI
Identification of a cold receptor reveals a general role for TRP channels in thermosensation
TL;DR: These findings, together with the previous identification of the heat-sensitive channels VR1 and VRL-1, demonstrate that TRP channels detect temperatures over a wide range and are the principal sensors of thermal stimuli in the mammalian peripheral nervous system.
Journal ArticleDOI
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
TL;DR: A comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy is provided.
References
More filters
Journal ArticleDOI
The capsaicin receptor: a heat-activated ion channel in the pain pathway
Michael J. Caterina,Mark Schumacher,Makoto Tominaga,Tobias A. Rosen,Jon D. Levine,David Julius +5 more
TL;DR: The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo.
Journal ArticleDOI
Isolation and structure of a brain constituent that binds to the cannabinoid receptor
William A. Devane,Lumir Hanus,Aviva Breuer,Roger G. Pertwee,Lesley A. Stevenson,Graeme Griffin,Dan Gibson,Asher Mandelbaum,A. Etinger,Raphael Mechoulam +9 more
TL;DR: In this article, an arachidonylethanthanolamide (anandamide) was identified in a screen for endogenous ligands for the cannabinoid receptor and its structure was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and confirmed by synthesis.
Journal ArticleDOI
The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli
Makoto Tominaga,Michael J. Caterina,Annika B. Malmberg,Tobias A. Rosen,Heather Gilbert,Kate Skinner,Brigitte E Raumann,Allan I. Basbaum,David Julius +8 more
TL;DR: It is shown that protons decrease the temperature threshold for VR1 activation such that even moderately acidic conditions (pH < or = 5.9) activate VR1 at room temperature, and VR1 can be viewed as a molecular integrator of chemical and physical stimuli that elicit pain.
Journal Article
Vanilloid (Capsaicin) Receptors and Mechanisms
Arpad Szallasi,Peter M. Blumberg +1 more
TL;DR: This paper focuses on hot pepper, which is eaten on a daily basis by an estimated one-quarter of the world’s population and has potential to be a biological target for regenerative medicine.
Journal ArticleDOI
Pharmacology of cannabinoid cb1 and cb2 receptors
TL;DR: This review focuses on the classification, binding properties, effector systems and distribution of cannabinoid receptors, and describes the various cannabinoid receptor agonists and antagonists now available and considers the main in vivo and in vitro bioassay methods that are generally used.