Golech Susanne Andrea, McCarron Richard M, Chen Ye, Bembry Joliet, Lenz Frederick, Mechoulam Raphael, Shohami Esther, Spatz Maria
Resuscitative Medicine Department, Naval Medical Research Center, Bethesda, MD, USA.
Brain Res Mol Brain Res. 2004 Dec 6;132(1):87-92. doi: 10.1016/j.molbrainres.2004.08.025.
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.
花生四烯酸衍生物2-花生四烯酸甘油酯（2-AG）最初是从肠道和大脑中分离出来的；它也由血液和血管细胞产生并释放。许多由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。本文呈现的研究结果证明了CB1、CB2和TRPV1受体在脑微血管内皮细胞（HBEC）上的表达。分别通过逆转录聚合酶链反应（RT-PCR）和多克隆抗体证实了TRPV1、CB1和CB2受体mRNA及蛋白的表达。内源性大麻素2-AG以及其他相关化合物[花生四烯乙醇胺（ANA）、甲基花生四烯乙醇胺（m-ANA）、N-（4-羟基苯基-花生四烯酰基-乙醇酰胺）（AM404）和辣椒素]在HBEC中呈剂量依赖性地刺激钙离子内流。选择性TRPV1受体拮抗剂（辣椒平）、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（TRPV1受体的特异性激动剂）的作用被辣椒平抑制，但仅被CB1或CB2受体拮抗剂微弱抑制。2-AG还诱导了血管舒张刺激磷蛋白（VASP）的磷酸化；这种反应由VR1受体介导。这些研究清楚地表明，2-AG和其他相关化合物可能作为VR1受体以及CB1和CB2受体的激动剂发挥作用，并表明这些因素参与了HBEC的各种功能。
