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Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor.
Mol Pharmacol. 2003 Mar; 63(3):699-705.MP

Abstract

The cannabinoid analog abnormal cannabidiol [abn-cbd; (-)-4-(3-3,4-trans-p-menthadien-[1,8]-yl)-olivetol] does not bind to CB(1) or CB(2) 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 BK(Ca) channel inhibitor charybdotoxin, but not by the nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester or by the vanilloid VR1 receptor antagonist capsazepine. The cannabidiol analog O-1918 does not bind to CB(1) or CB(2) receptors and does not cause vasorelaxation at concentrations up to 30 microM, but it does cause concentration-dependent (1-30 microM) 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 CB(1) receptor agonist (-)-11-OH-Delta(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 CB(1) or CB(2) receptors and is coupled through G(i)/G(o) to the PI3 kinase/Akt signaling pathway.

Authors+Show Affiliations

Laboratory of Physiologic Studies, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Bethesda, Maryland, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comment
Journal Article

Language

eng

PubMed ID

12606780

Citation

Offertáler, László, et al. "Selective Ligands and Cellular Effectors of a G Protein-coupled Endothelial Cannabinoid Receptor." Molecular Pharmacology, vol. 63, no. 3, 2003, pp. 699-705.
Offertáler L, Mo FM, Bátkai S, et al. Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Mol Pharmacol. 2003;63(3):699-705.
Offertáler, L., Mo, F. M., Bátkai, S., Liu, J., Begg, M., Razdan, R. K., Martin, B. R., Bukoski, R. D., & Kunos, G. (2003). Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Molecular Pharmacology, 63(3), 699-705.
Offertáler L, et al. Selective Ligands and Cellular Effectors of a G Protein-coupled Endothelial Cannabinoid Receptor. Mol Pharmacol. 2003;63(3):699-705. PubMed PMID: 12606780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. AU - Offertáler,László, AU - Mo,Fong-Ming, AU - Bátkai,Sándor, AU - Liu,Jie, AU - Begg,Malcolm, AU - Razdan,Raj K, AU - Martin,Billy R, AU - Bukoski,Richard D, AU - Kunos,George, PY - 2003/2/28/pubmed PY - 2003/5/13/medline PY - 2003/2/28/entrez SP - 699 EP - 705 JF - Molecular pharmacology JO - Mol Pharmacol VL - 63 IS - 3 N2 - The cannabinoid analog abnormal cannabidiol [abn-cbd; (-)-4-(3-3,4-trans-p-menthadien-[1,8]-yl)-olivetol] does not bind to CB(1) or CB(2) 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 BK(Ca) channel inhibitor charybdotoxin, but not by the nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester or by the vanilloid VR1 receptor antagonist capsazepine. The cannabidiol analog O-1918 does not bind to CB(1) or CB(2) receptors and does not cause vasorelaxation at concentrations up to 30 microM, but it does cause concentration-dependent (1-30 microM) 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 CB(1) receptor agonist (-)-11-OH-Delta(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 CB(1) or CB(2) receptors and is coupled through G(i)/G(o) to the PI3 kinase/Akt signaling pathway. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/12606780/Selective_ligands_and_cellular_effectors_of_a_G_protein_coupled_endothelial_cannabinoid_receptor_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12606780 DB - PRIME DP - Unbound Medicine ER -