![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 63, Issue 3, 699-705, March 2003
Laboratory of Physiologic Studies, National Institute on Alcoholism
and Alcohol Abuse, National Institutes of Health, Bethesda, Maryland
(L.O., S.B., J.L., M.B., G.K.); Organix, Inc., Woburn, Massachusetts
(R.K.R.); Department of Pharmacology and Toxicology, Virginia
Commonwealth University, Richmond, Virginia (B.R.M.); and
Cardiovascular Disease Research Program, North Carolina Central
University, Durham, North Carolina (R.D.B.)
The cannabinoid analog abnormal cannabidiol [abn-cbd;
(
)-4-(3-3,4-trans-p-menthadien-[1,8]-yl)-olivetol]
does not bind to CB1 or CB2 receptors, yet it
acts as a full agonist in relaxing rat isolated mesenteric artery
segments. Vasorelaxation by abn-cbd is endothelium-dependent, pertussis
toxin-sensitive, and is inhibited by the BKCa channel
inhibitor charybdotoxin, but not by the nitric-oxide synthase
inhibitor N
-nitro-L-arginine
methyl ester or by the vanilloid VR1 receptor antagonist capsazepine.
The cannabidiol analog O-1918 does not bind to CB1 or
CB2 receptors and does not cause vasorelaxation at
concentrations up to 30 µM, but it does cause concentration-dependent (1-30 µM) inhibition of the vasorelaxant effects of abn-cbd and anandamide. In anesthetized mice, O-1918 dose-dependently inhibits the
hypotensive effect of abn-cbd but not the hypotensive effect of the
CB1 receptor agonist
()-11-OH-
9-tetrahydrocannabinol dimethylheptyl. In
human umbilical vein endothelial cells, abn-cbd induces phosphorylation
of p42/44 mitogen-activated protein kinase and protein kinase B/Akt,
which is inhibited by O-1918, by pertussis toxin or by
phosphatidylinositol 3 (PI3) kinase inhibitors. These findings indicate
that abn-cbd is a selective agonist and that O-1918 is a selective,
silent antagonist of an endothelial "anandamide receptor", which is
distinct from CB1 or CB2 receptors and is
coupled through Gi/Go to the PI3 kinase/Akt signaling pathway.
This article has been cited by other articles:
|
|
 |
|
  M. Waldeck-Weiermair, C. Zoratti, K. Osibow, N. Balenga, E. Goessnitzer, M. Waldhoer, R. Malli, and W. F. Graier Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression J. Cell Sci., May 15, 2008; 121(10): 1704 - 1717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, J. F. Wang, G. Kunos, and J. E. Groopman Cannabinoid Modulation of Kaposi's Sarcoma Associated Herpesvirus Infection and Transformation Cancer Res., August 1, 2007; 67(15): 7230 - 7237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. McCollum, A. C. Howlett, and S. Mukhopadhyay Anandamide-Mediated CB1/CB2 Cannabinoid Receptor-Independent Nitric Oxide Production in Rabbit Aortic Endothelial Cells J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 930 - 937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Giudice, L. Rinaldi, M. Passarotto, F. Facchinetti, A. D'Arrigo, A. Guiotto, M. D. Carbonare, L. Battistin, and A. Leon Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells J. Leukoc. Biol., June 1, 2007; 81(6): 1512 - 1522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Straiker and K. Mackie Metabotropic suppression of excitation in murine autaptic hippocampal neurons J. Physiol., February 1, 2007; 578(3): 773 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. KYROU, G. VALSAMAKIS, and C. TSIGOS The Endocannabinoid System as a Target for the Treatment of Visceral Obesity and Metabolic Syndrome Ann. N.Y. Acad. Sci., November 1, 2006; 1083(1): 270 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, S. Batkai, and G. Kunos The Endocannabinoid System as an Emerging Target of Pharmacotherapy Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Rao and N. E. Kaminski Cannabinoid-Mediated Elevation of Intracellular Calcium: A Structure-Activity Relationship J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 820 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Milman, Y. Maor, S. Abu-Lafi, M. Horowitz, R. Gallily, S. Batkai, F.-M. Mo, L. Offertaler, P. Pacher, G. Kunos, et al. N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties PNAS, February 14, 2006; 103(7): 2428 - 2433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Awumey, A. C. Howlett, and D. I. Diz Is there a role for anandamide in cardiovascular regulation? Insights from studies of endocannabinoid metabolism Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H520 - H521. [Full Text] [PDF]
|
|
|
|
|
|
D. J. Rademacher, S. Patel, W.-S. V. Ho, A. M. Savoie, N. J. Rusch, K. M. Gauthier, and C. J. Hillard U-46619 but not serotonin increases endocannabinoid content in middle cerebral artery: evidence for functional relevance Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2694 - H2701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mishima, K. Hayakawa, K. Abe, T. Ikeda, N. Egashira, K. Iwasaki, and M. Fujiwara Cannabidiol Prevents Cerebral Infarction Via a Serotonergic 5-Hydroxytryptamine1A Receptor-Dependent Mechanism Stroke, May 1, 2005; 36(5): 1071 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Batkai, P. Pacher, D. Osei-Hyiaman, S. Radaeva, J. Liu, J. Harvey-White, L. Offertaler, K. Mackie, M. A. Rudd, R. D. Bukoski, et al. Endocannabinoids Acting at Cannabinoid-1 Receptors Regulate Cardiovascular Function in Hypertension Circulation, October 5, 2004; 110(14): 1996 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Batkai, P. Pacher, Z. Jarai, J. A. Wagner, and G. Kunos Cannabinoid antagonist SR-141716 inhibits endotoxic hypotension by a cardiac mechanism not involving CB1 or CB2 receptors Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H595 - H600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Begg, F.-M. Mo, L. Offertaler, S. Batkai, P. Pacher, R. K. Razdan, D. M. Lovinger, and G. Kunos G Protein-coupled Endothelial Receptor for Atypical Cannabinoid Ligands Modulates a Ca2+-dependent K+ Current J. Biol. Chem., November 14, 2003; 278(46): 46188 - 46194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, S. Batkai, P. Pacher, J. Harvey-White, J. A. Wagner, B. F. Cravatt, B. Gao, and G. Kunos Lipopolysaccharide Induces Anandamide Synthesis in Macrophages via CD14/MAPK/Phosphoinositide 3-Kinase/NF-{kappa}B Independently of Platelet-activating Factor J. Biol. Chem., November 7, 2003; 278(45): 45034 - 45039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Franklin, S. Parmentier-Batteur, L. Walter, D. A. Greenberg, and N. Stella Palmitoylethanolamide Increases after Focal Cerebral Ischemia and Potentiates Microglial Cell Motility J. Neurosci., August 27, 2003; 23(21): 7767 - 7775. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
