′Entourage′ effects of N-palmitoylethanolamide and N-oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptors
′Entourage′ effects of N-palmitoylethanolamide and N-oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptors
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DOI：
10.1038/bjp.2008.324
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发表时间：
2008-11-01
影响因子：
7.3
通讯作者：
Randall, M. D.
中科院分区：
文献类型：
--
作者：
Ho, W-S V.;Barrett, D. A.;Randall, M. D.
背景和目的：内源性大麻素 N-花生四烯酰乙醇酰胺 (anandamide) 与其他 N-酰基乙醇酰胺，即 N-棕榈酰乙醇酰胺 (PEA) 和 N-油酰乙醇酰胺 (OEA) 共同合成，它们已被证明可以增强非血管组织中的 anandamide 反应（所谓的“随行效应”）。目前尚不清楚这种相互作用是否发生在循环中。 实验方法：在大鼠离体小肠系膜动脉中，在肌电图条件下检查 PEA 和 OEA 对 anandamide 松弛的影响以及 N-酰基乙醇酰胺的组织含量。 主要结果：用 PEA (10 μM) 或 OEA (1 μM) 或联合预处理可增强 Anandamide 诱导的松弛。 PEA 和 OEA 的增强作用不依赖于内皮细胞，并且可通过辣椒素 (10 mM) 或 TRPV1 受体拮抗剂 N-(3-甲氧基苯基)-4-氯肉桂酰胺 (SB366791) (2 mM) 治疗消除，辣椒素可使瞬时受体电位 1 型香草酸 (TRPV1) 受体系统脱敏。还观察到 anandamide 和 PEA（或 OEA）的摩尔比与肠系膜动脉中的摩尔比相似。 PEA 和 3'-氨基甲酰基-联苯-3-基-环己基氨基甲酸酯 (URB597) (1 μM) 对 anandamide 水解的抑制额外增强了 anandamide 反应。另一方面，PEA 和 OEA 本身也诱导血管舒张（效力排序：anandamide > OEA > PEA），但三种 N-酰基乙醇酰胺的舒张作用对辣椒素、SB366791 和 URB597 治疗表现出不同的敏感性。例如，辣椒素和 SB366791 均减弱了对 anandamide 和 OEA 的松弛作用，但对 PEA 没有作用。 结论和意义：本研究表明，PEA 和 OEA 通过大鼠肠系膜小动脉中的 TRPV1 受体增强对 anandamide 的松弛反应。这些同源物本身也诱导血管舒张，表明 N-酰基乙醇酰胺具有血管控制功能。
Background and purpose: The endocannabinoid N-arachidonoylethanolamide (anandamide) is co-synthesized with other N-acylethanolamides, namely N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA), which have been shown to potentiate anandamide responses (so-called ' entourage effects') in non-vascular tissues. It remains unclear whether such interactions occur in the circulation.Experimental approach: In rat isolated small mesenteric arteries, the effects of PEA and OEA on relaxation to anandamide and tissue contents of the N-acylethanolamides were examined under myographic conditions.Key results: Anandamide-induced relaxation was potentiated by pretreatment with PEA (10 mu M) or OEA (1 mu M), or in combination. The potentiation by PEA and OEA was endothelium-independent and abolished by treatment with capsaicin ( 10 mM), which desensitizes the transient receptor potential vanilloid type 1 (TRPV1) receptor system, or by the TRPV1 receptor antagonist, N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791) ( 2 mM). It was also observed at molar ratios of anandamide and PEA ( or OEA) similar to those found in mesenteric arteries. PEA and inhibition of anandamide hydrolysis by 3 '-carbamoyl-biphenyl-3- yl-cyclohexylcarbamate (URB597) (1 mu M) additively potentiated anandamide responses. On the other hand, PEA and OEA also induced vasorelaxation per se (rank order of potency: anandamide > OEA > PEA), but relaxation to the three N-acylethanolamides displayed different sensitivity to treatment with capsaicin, SB366791 and URB597. For example, relaxations to anandamide and OEA, but not PEA, were attenuated by both capsaicin and SB366791.Conclusion and implications: This study shows that PEA and OEA potentiate relaxant responses to anandamide through TRPV1 receptors in rat small mesenteric arteries. The congeners also induce vasorelaxation per se, suggesting a function for the N- acylethanolamides in vascular control.