Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy.
Curr Neurovasc Res. 2010 Nov;7(4):311-8. doi: 10.2174/156720210793180774.
In the last decade, the neurovascular effects exerted by endocannabinoids (eCBs) have attracted growing interest, because they hold the promise to open new avenues of therapeutic intervention against major causes of death in Western society. Several actions of eCBs are mediated by type-1 (CB₁) or type-2 (CB₂) cannabinoid receptors, yet there is no clear evidence of the presence of these proteins in platelets. To demonstrate that CB₁ and CB₂ are expressed in human platelets, we analyzed their protein level by Western blotting and ELISA, visualized their cellular localization by confocal microscopy, and ascertained their functionality by binding assays. We found that CB₁, and to a lesser extent CB₂, are expressed in highly purified human platelets. Both receptor subtypes were predominantly localized inside the cell, thus explaining why they might remain undetected in preparations of plasma membranes. The identification of authentic CB₁ and CB₂ in human platelets supports the potential exploitation of selective agonists or antagonists of these receptors as novel therapeutics to combat neurovascular disorders. It seems remarkable that some of these substances have been already used in humans to treat disease states.
在过去的十年中,内源性大麻素(eCBs)发挥的神经血管效应引起了越来越多的关注,因为它们有望为治疗西方社会主要死亡原因开辟新的途径。eCB 的几种作用是通过 1 型(CB₁)或 2 型(CB₂)大麻素受体介导的,然而,在血小板中不存在这些蛋白的明确证据。为了证明 CB₁ 和 CB₂ 在人血小板中表达,我们通过 Western blot 和 ELISA 分析其蛋白水平,通过共聚焦显微镜观察其细胞定位,并通过结合测定确定其功能。我们发现 CB₁,在较小程度上还有 CB₂,在高度纯化的人血小板中表达。这两种受体亚型主要定位于细胞内,这解释了为什么它们可能在血浆膜制剂中未被检测到。在人血小板中鉴定出真正的 CB₁ 和 CB₂ 支持了这些受体的选择性激动剂或拮抗剂作为治疗神经血管疾病的新型治疗剂的潜在应用。值得注意的是,其中一些物质已经在人类中用于治疗疾病状态。