N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor.
N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor.
复制标题
N-花生四烯乙醇酰胺对牛冠状动脉的松弛作用不是由 CB1 大麻素受体介导的。
DOI：
10.1152/ajpheart.1998.274.1.h375
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Campbell,WB
中科院分区：
文献类型：
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作者：
Pratt,PF;Hillard,CJ;Edgemond,WS;Campbell,WB
内源性大麻素N-花生四烯酸乙醇酰胺（AEA），通常简称大麻素，在大鼠肠系膜动脉中具有内皮源性超极化因子的特性。我们已经进行了研究，以确定是否AEA影响冠状动脉血管紧张度。在用U-46619（3 × 10− 9 M）预收缩的离体牛冠状动脉环中测定AEA的血管舒张作用。AEA降低等长收缩张力，在10− 5 M浓度下产生51 ± 9%的最大松弛。AEA对内皮剥脱的冠状动脉无明显影响。CB 1受体拮抗剂SR-141716 A（10− 6 M）未能降低AEA的血管舒张作用，表明CB 1受体不参与AEA的这种作用。由于AEA在大脑和肝脏中通过脂肪酸酰胺水解酶（FAAH）快速转化为花生四烯酸和乙醇胺，我们假设AEA的血管舒张作用是由其水解为花生四烯酸，然后酶促转化为血管舒张类花生酸引起的。为了支持这一假设，牛冠状动脉与[3 H]AEA孵育30分钟水解15%的添加底物;约9%的放射性标记产物为游离花生四烯酸，6%与异戊四烯酸（PG）和环氧二十碳三烯酸（EEA）共迁移。在培养的牛冠状动脉内皮细胞中获得了类似的结果。用重氮甲基花生四烯酸酮抑制FAAH，可阻断[~ 3 H]AEA的代谢和对AEA的舒张作用。用[3 H]花生四烯酸预标记的全血管和培养的内皮细胞对A-23187产生反应，合成[3 H] PG和[3 H] EEA，但不合成[3 H]AEA。此外，SR-141716 A减弱了A-23187刺激的[3 H]花生四烯酸释放，表明其可能具有除抑制CB 1受体以外的作用。这些实验表明，AEA产生内皮依赖性血管舒张，这是由于其催化花生四烯酸，然后转化为血管舒张性类二十烷酸，如前列环素或雌二醇。
It has been reported that the endogenous cannabinoidN-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 × 10−9M). AEA decreased isometric tension, producing a maximal relaxation of 51 ± 9% at a concentration of 10−5M. Endothelium-denuded coronary arteries were not significantly affected by AEA. The CB1 receptor antagonist SR-141716A (10−6M) 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; ∼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.