| Résumé | The effects of vasoactive peptides endothelins (ET-1, ET-2, ET-3, S6b, S6c) on release of 51Cr, production of inositol triphosphate (IP3), and release of arachidonic acid (AA) were examined in cultured microvascular endothelium derived from human brain (HBEC). ET-1 induced dose-dependent release of 51Cr (EC50= 7 ± 2 nM), transient increase of 1P3 (EC50= 0.67±0.09 nM), and sustained release of AA (EC50 = 59 ± 7 nM) from HBEC. Under the same experimental conditions, viability of the cells was preserved (>97%) as assessed by exclusion of vital dye trypan blue and release of lactate dehydrogenase (LDH). Dexamethasone (1 μM) inhibited ET-1-induced AA release, whereas it was ineffective on 51Cr release. Protein kinase C (PKC) inhibitor H7 (200 nM), calcium channel blocker verapamil (10 μM), or 1P3 receptor antagonist ryonidine (5 μM) reduced ET-1 (100 μM)-induced release of 51Cr. These findings indicate that endothelins can induce an increase of HBEC permeability by a receptor-specific activation of PKC and intracellular calcium mobilization. |
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