Human brain endothelium: coexpression and function of vanilloid and endocannabinoid receptors
Human brain endothelium: coexpression and function of vanilloid and endocannabinoid receptors
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DOI：
10.1016/j.molbrainres.2004.08.025
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发表时间：
2004-12-06
期刊：
影响因子：
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通讯作者：
Spatz, M
中科院分区：
文献类型：
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作者：
Golech, SA;McCarron, RM;Spatz, M
花生四烯酸衍生物2-花生四烯酰甘油（2-AG）最初从肠道和脑中分离得到；它也从血液和血管细胞中产生和释放。许多2- ag诱导的细胞反应（即神经调节、细胞保护和血管舒张）是由大麻素受体CB1和CB2介导的。本研究结果证实了CB1、CB2和TRPV1受体在脑血管内皮细胞（HBEC）上的表达。RT-PCR和多克隆抗体分别检测了TRPV1、CB1和CB2受体mRNA和蛋白的表达。内源性大麻素2-AG和其他相关化合物[anandamide (ANA), methanandamide (m-ANA), N-（4-羟基苯基-花生四烯基-乙醇酰胺）（AM404）和辣椒素]剂量依赖性地刺激HBEC中的Ca2+内流。选择性TRPV1受体拮抗剂（capsazepine）、CB1受体拮抗剂（SR141716A）和CB2受体拮抗剂（SR144528）抑制了这些反应。辣椒素是TRPV1受体的特异性激动剂，其作用可被辣椒平抑制，但CB1或CB2受体拮抗剂的作用较弱。2-AG还能诱导血管扩张剂刺激磷酸化（VASP）；这种反应是由VR1受体介导的。这些研究清楚地表明，2-AG等相关化合物可能作为激动剂作用于VR1受体，以及CB1和CB2受体，并暗示这些因子参与了HBEC的各种功能。Elsevier B.V.出版
The arachidonic acid derivative, 2-arachidonoyl-glycerol (2-AG), was initially isolated from gut and brain; it is also produced and released from blood and vascular cells. Many of the 2-AG-induced cellular responses (i.e., neuromodulation, cytoprotection and vasodilation) are mediated by cannabinoid receptors CB1 and CB2. The findings presented here demonstrate the expression of CB1, CB2 and TRPV1 receptors on cerebromicrovascular endothelial cells (HBEC). The expression of TRPV1, CB1 and CB2 receptor mRNA and proteins were demonstrated by RT-PCR and polyclonal antibodies, respectively. The endocannabinoid 2-AG, and other related compounds [anandamide (ANA), methanandamide (m-ANA), N-(4-hydroxyphenyl-arachidonyl-ethanolamide) (AM404) and capsaicin] dose-dependently stimulated Ca2+ influx in HBEC. The selective TRPV1 receptor antagonist (capsazepine), CB1 receptor antagonist (SR141716A) and CB2 receptor antagonist (SR144528) inhibited these responses. The effects of capsaicin, a specific agonist for TRPV1 receptors, were inhibited by capsazepine, but only weakly by CB1 or CB2 receptor antagonists. 2-AG also induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP); this response was mediated by VR1 receptors. These studies clearly indicate that 2-AG and other related compounds may function as agonists on VR1 receptors, as well as CB1 and CB2 receptors, and implicated these factors in various HBEC functions. Published by Elsevier B.V.