Greeno E W, Mantyh P, Vercellotti G M, Moldow C F
Department of Medicine, University of Minnesota, Minneapolis.
J Exp Med. 1993 May 1;177(5):1269-76. doi: 10.1084/jem.177.5.1269.
Substance P (SP), a neurotachykinin, is important in a number of inflammatory processes in which the endothelial cell also plays a critical role. SP receptors have previously been identified only on arterial endothelium, and the scant in vitro evidence for direct effects of SP on human endothelium is based on studies using nonarterial cells. To better understand SP's role in inflammation, we sought to identify functional SP receptors on human endothelium in situ and in culture. Autoradiographic ligand binding to human umbilical cord sections demonstrates the presence of SP binding sites with characteristics of the neurokinin 1 (NK-1) receptor (displacement by GTP analogues and the NK-1 specific antagonist CP-96,345) on human umbilical arterial, but not venous, endothelium. In culture, human umbilical venous endothelial cells (HUVECs) and human aortic endothelial cells express low levels of available SP binding sites. However, HUVECs, which are serum starved and refed, undergo a dramatic increase in SP binding. SP binding to starved/refed HUVECs induces a transient increase in intracellular calcium. This calcium flux is dose dependent over appropriate SP concentrations and can be blocked by NK-1 specific antagonists. The proinflammatory effects of SP may be mediated in part through the NK-1 receptor on endothelium.
P物质（SP）是一种神经速激肽，在许多炎症过程中起重要作用，而内皮细胞在这些过程中也起着关键作用。SP受体以前仅在动脉内皮上被发现，而且关于SP对人内皮细胞直接作用的体外证据很少，这些证据是基于使用非动脉细胞的研究。为了更好地理解SP在炎症中的作用，我们试图在原位和培养状态下鉴定人内皮细胞上的功能性SP受体。放射自显影配体与人脐带切片结合显示，在人脐动脉而非静脉内皮上存在具有神经激肽1（NK-1）受体特征的SP结合位点（被GTP类似物和NK-1特异性拮抗剂CP-96,345取代）。在培养中，人脐静脉内皮细胞（HUVECs）和人主动脉内皮细胞表达低水平的可用SP结合位点。然而，血清饥饿后再补给的HUVECs，其SP结合显著增加。SP与饥饿/再补给的HUVECs结合会导致细胞内钙的短暂增加。在适当的SP浓度范围内，这种钙通量是剂量依赖性的，并且可以被NK-1特异性拮抗剂阻断。SP的促炎作用可能部分通过内皮上的NK-1受体介导。
