Abstract
Human cerebromicrovascular endothelial cells (HBEC) in culture express high affinity ET A receptors coupled to phospholipase C activation. Pretreatment of HBEC with 1 μM dexamethasone for 24 h decreased the number of the ET-1 binding sites (B max) 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 (IP 3) production, whereas half-maximal stimulatory concentration (EC 50) 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 IP 3 production was abolished by glucocorticoid-receptor antagonist cortexolone. In contrast, vasopressin-mediated IP 3 response in HBEC was not changed by dexamethasone. Cyclo-oxygenase inhibitors indomethacin and acetylsalicylic acid did not influence the ET-1-induced IP 3 production by HBEC. The down-regulation of ET A 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).
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