Stanimirovic D B, McCarron R M, Spatz M
Stroke Branch, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Neuropeptides. 1994 Mar;26(3):145-52. doi: 10.1016/0143-4179(94)90123-6.
Human cerebromicrovascular endothelial cells (HBEC) in culture express high affinity ETA receptors coupled to phospholipase C activation. Pretreatment of HBEC with 1 microM dexamethasone for 24 h decreased the number of the ET-1 binding sites (Bmax) on HBEC (96 fmol/mg protein vs 57 fmol/mg protein) without changing the binding affinity (KD) (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 half-maximal stimulatory concentration (EC50) was not affected. This effect of dexamethasone was concentration-dependent, and most pronounced after 24 h of pretreatment. The inhibitory effect of dexamethasone on the ET-1-induced IP3 production was abolished by glucocorticoid-receptor antagonist cortexolone. In contrast, vasopressin-mediated IP3 response in HBEC was not changed by dexamethasone. Cyclo-oxygenase 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).
培养的人脑微血管内皮细胞（HBEC）表达与磷脂酶C激活偶联的高亲和力ETA受体。用1微摩尔/升地塞米松预处理HBEC 24小时，可减少HBEC上ET-1结合位点的数量（Bmax）（从96飞摩尔/毫克蛋白降至57飞摩尔/毫克蛋白），而不改变结合亲和力（KD）（101皮摩尔对92皮摩尔）或置换曲线（ET-1 = ET-2 > ET-3 > S6c）。地塞米松预处理的HBEC在最大ET-1刺激的肌醇三磷酸（IP3）产生方面也表现出40%的降低，而半最大刺激浓度（EC50）不受影响。地塞米松的这种作用具有浓度依赖性，且在预处理24小时后最为明显。地塞米松对ET-1诱导的IP3产生的抑制作用可被糖皮质激素受体拮抗剂皮质酮消除。相比之下，地塞米松并未改变HBEC中血管加压素介导的IP3反应。环氧化酶抑制剂吲哚美辛和乙酰水杨酸不影响HBEC中ET-1诱导的IP3产生。地塞米松对HBEC中ETA受体的下调可能代表了糖皮质激素对脑微血管功能的上述影响（即血脑屏障特性的改变、血管活性因子的分泌、血管形态发生）所涉及的机制之一。
