HUMAN CEREBROMICROVASCULAR ENDOTHELIAL RECEPTORS

人脑微血管内皮细胞在培养中的表达 高亲和力ET/A受体与磷脂酶C(PLC)激活偶联。 1微米地塞米松处理HBEC 24小时可降低HEC的存活率 HBEC上ET-1结合位点(Bmax)的数量(96fmol-mg蛋白vs.57 Fmol-mg蛋白_)，而不改变结合亲和力(K/D)(101 pm vs. 92 PM)或移位轮廓(ET-1=ET-2&gt；ET-3&gt；S6c)。地塞米松- 经HBEC处理后，最大ET-1也降低了40% 刺激三磷酸肌醇(IP3)的产生，而一半- 最大刺激浓度(EC50)不受影响。这一效果 地塞米松的作用呈浓度依赖性，在 24小时的预处理。地塞米松对ET-1的抑制作用 糖皮质激素受体可取消1诱导的IP3产生 拮抗剂皮质醇。相反，加压素介导的IP3反应 地塞米松不影响HBEC的活性。环氧合酶抑制剂， 吲哚美辛和乙酰水杨酸不影响ET-1诱导的 HBEC生产IP3。人脐静脉内皮细胞ETA受体表达下调 地塞米松可能代表了一种涉及所述 糖皮质激素对脑微血管功能的影响(即， 血脑屏障性质、血管活性物质分泌的变化 因素、血管形态发生等)。

Human cerebromicrovascular endothelial cells (HBEC) in culture express high affinity ET/A receptors coupled to phospholipase C (PLC) activation. Pretreatment of HBEC with 1 microM dexamethasone for 24 hr decreased the number of ET-1 binding sites (Bmax) on HBEC (96 fmol-mg protein vs. 57 fmol-mg protein_) without changing the binding affinity (K/D) (101 pm vs. 92 pM) or displacing profile (ET-1= ET-2>ET-3 >S6c). Dexamethasone- pretreated HBEC also exhibited a 40% reduction in the maximal ET-1 stimulated inositol triphosphate (IP3) production, whereas the half- maximal stimulatory concentration (EC50) was not affected. This effect of dexamethasone was concentration-dependent and most pronounced after 24 hr of pretreatment. The inhibitory effect of dexamethasone on the ET- 1-induced IP3 production was abolished by the glucocorticoid receptor antagonist cortexolone. In contrast, vasopressin-mediated IP3 response in HBEC was not changed by dexamethasone. The cyclooxygenase inhibitors, indomethacin and acetylsalicylic acid, did not influence the ET-1-induced IP3 production by HBEC. The down-regulation of ETA receptors in HBEC by dexamethasone may represent one of the mechanisms involving the described effects of glucocorticoids on cerebromicrovascular function (i.e., changes in blood-brain barrier properties, secretion of vasoactive factors, vascular morphogenesis, etc.).