Biomaterial Database

Dexamethasone down-regulates endothelin receptors in human cerebromicrovascular endothelial cells. 1994

D B Stanimirovic, and R M McCarron, and M Spatz

Stroke Branch, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

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).

UI	MeSH Term	Description	Entries
D007293	Inosine Triphosphate	Inosine 5'-(tetrahydrogen triphosphate). An inosine nucleotide containing three phosphate groups esterified to the sugar moiety. Synonym: IRPPP.	ITP,Triphosphate, Inosine
D007294	Inositol	An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction.	Myoinositol,Chiro-Inositol,Mesoinositol,Chiro Inositol
D007457	Iodine Radioisotopes	Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.	Radioisotopes, Iodine
D011965	Receptors, Glucocorticoid	Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example.	Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D002196	Capillaries	The minute vessels that connect arterioles and venules.	Capillary Beds,Sinusoidal Beds,Sinusoids,Bed, Sinusoidal,Beds, Sinusoidal,Capillary,Capillary Bed,Sinusoid,Sinusoidal Bed
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D002560	Cerebrovascular Circulation	The circulation of blood through the BLOOD VESSELS of the BRAIN.	Brain Blood Flow,Regional Cerebral Blood Flow,Cerebral Blood Flow,Cerebral Circulation,Cerebral Perfusion Pressure,Circulation, Cerebrovascular,Blood Flow, Brain,Blood Flow, Cerebral,Brain Blood Flows,Cerebral Blood Flows,Cerebral Circulations,Cerebral Perfusion Pressures,Circulation, Cerebral,Flow, Brain Blood,Flow, Cerebral Blood,Perfusion Pressure, Cerebral,Pressure, Cerebral Perfusion
D003348	Cortisone	A naturally occurring glucocorticoid that has been used in replacement therapy for ADRENAL INSUFFICIENCY and as an anti-inflammatory agent. Cortisone itself is inactive; it is converted in the liver to the active metabolite HYDROCORTISONE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p726)	17-Hydroxy-3,11,20-trioxopregn-4-en-21-yl acetate,Adreson,Cortisone Acetate,Cortone Acetate
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums