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N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor.
Am J Physiol. 1998 01; 274(1):H375-81.AJ

Abstract

It has been reported that the endogenous cannabinoid N-arachidonylethanolamide (AEA), commonly referred to as anandamide, has the characteristics of an endothelium-derived hyperpolarizing factor in rat mesenteric artery. We have carried out studies to determine whether AEA affects coronary vascular tone. The vasorelaxant effects of AEA were determined in isolated bovine coronary artery rings precontracted with U-46619 (3 x 10(-9) M). AEA decreased isometric tension, producing a maximal relaxation of 51 +/- 9% at a concentration of 10(-5) M. Endothelium-denuded coronary arteries were not significantly affected by AEA. The CB1 receptor antagonist SR-141716A (10(-6)M) failed to reduce the vasodilatory effects of AEA, suggesting that the CB1 receptor is not involved in this action of AEA. Because AEA is rapidly converted to arachidonic acid and ethanolamine in brain and liver by a fatty acid amide hydrolase (FAAH), we hypothesized that the vasodilatory effect of AEA results from its hydrolysis to arachidonic acid followed by enzymatic conversion to vasodilatory eicosanoids. In support of this hypothesis, bovine coronary arteries incubated with [3H]AEA for 30 min hydrolyzed 15% of added substrate; approximately 9% of the radiolabeled product was free arachidonic acid, and 6% comigrated with the prostaglandins (PGs) and epoxyeicosatrienoic acids (EETs). A similar result was obtained in cultured bovine coronary endothelial cells. Inhibition of the FAAH with diazomethylarachidonyl ketone blocked both the metabolism of [3H]AEA and the relaxations to AEA. Whole vessel and cultured endothelial cells prelabeled with [3H]arachidonic acid synthesized [3H]PGs and [3H]EETs, but not [3H]AEA, in response to A-23187. Furthermore, SR-141716A attenuated A-23187-stimulated release of [3H]arachidonic acid, suggesting that it may have actions other than inhibition of CB1 receptor. These experiments suggest that AEA produces endothelium-dependent vasorelaxation as a result of its catabolism to arachidonic acid followed by conversion to vasodilatory eicosanoids such as prostacyclin or the EETs.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9458889

Citation

Pratt, P F., et al. "N-arachidonylethanolamide Relaxation of Bovine Coronary Artery Is Not Mediated By CB1 Cannabinoid Receptor." The American Journal of Physiology, vol. 274, no. 1, 1998, pp. H375-81.
Pratt PF, Hillard CJ, Edgemond WS, et al. N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor. Am J Physiol. 1998;274(1):H375-81.
Pratt, P. F., Hillard, C. J., Edgemond, W. S., & Campbell, W. B. (1998). N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor. The American Journal of Physiology, 274(1), H375-81. https://doi.org/10.1152/ajpheart.1998.274.1.H375
Pratt PF, et al. N-arachidonylethanolamide Relaxation of Bovine Coronary Artery Is Not Mediated By CB1 Cannabinoid Receptor. Am J Physiol. 1998;274(1):H375-81. PubMed PMID: 9458889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor. AU - Pratt,P F, AU - Hillard,C J, AU - Edgemond,W S, AU - Campbell,W B, PY - 1998/2/12/pubmed PY - 1998/2/12/medline PY - 1998/2/12/entrez SP - H375 EP - 81 JF - The American journal of physiology JO - Am J Physiol VL - 274 IS - 1 N2 - It has been reported that the endogenous cannabinoid N-arachidonylethanolamide (AEA), commonly referred to as anandamide, has the characteristics of an endothelium-derived hyperpolarizing factor in rat mesenteric artery. We have carried out studies to determine whether AEA affects coronary vascular tone. The vasorelaxant effects of AEA were determined in isolated bovine coronary artery rings precontracted with U-46619 (3 x 10(-9) M). AEA decreased isometric tension, producing a maximal relaxation of 51 +/- 9% at a concentration of 10(-5) M. Endothelium-denuded coronary arteries were not significantly affected by AEA. The CB1 receptor antagonist SR-141716A (10(-6)M) failed to reduce the vasodilatory effects of AEA, suggesting that the CB1 receptor is not involved in this action of AEA. Because AEA is rapidly converted to arachidonic acid and ethanolamine in brain and liver by a fatty acid amide hydrolase (FAAH), we hypothesized that the vasodilatory effect of AEA results from its hydrolysis to arachidonic acid followed by enzymatic conversion to vasodilatory eicosanoids. In support of this hypothesis, bovine coronary arteries incubated with [3H]AEA for 30 min hydrolyzed 15% of added substrate; approximately 9% of the radiolabeled product was free arachidonic acid, and 6% comigrated with the prostaglandins (PGs) and epoxyeicosatrienoic acids (EETs). A similar result was obtained in cultured bovine coronary endothelial cells. Inhibition of the FAAH with diazomethylarachidonyl ketone blocked both the metabolism of [3H]AEA and the relaxations to AEA. Whole vessel and cultured endothelial cells prelabeled with [3H]arachidonic acid synthesized [3H]PGs and [3H]EETs, but not [3H]AEA, in response to A-23187. Furthermore, SR-141716A attenuated A-23187-stimulated release of [3H]arachidonic acid, suggesting that it may have actions other than inhibition of CB1 receptor. These experiments suggest that AEA produces endothelium-dependent vasorelaxation as a result of its catabolism to arachidonic acid followed by conversion to vasodilatory eicosanoids such as prostacyclin or the EETs. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/9458889/N_arachidonylethanolamide_relaxation_of_bovine_coronary_artery_is_not_mediated_by_CB1_cannabinoid_receptor_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.1998.274.1.H375?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -