Vasoactive peptides and prostaglandin D2 in human cerebromicrovascular endothelium

Prostaglandin D2 (PGD2) is the major prostanoid formed among other prostanoids in cultured microvascular endothelium derived from human brain (HBEC). Angiotensin II, arginine vasopressin and endothelium-1 stimulated the production of PGD2 and PGF2 alpha in a concentration-dependent manner, and this effect was inhibited by their specific receptor antagonists or dexamethasone (inhibitor of phospholipase A2/cyclooxygenase II). Both the peptidergic-induced PGD2 and the exogenously added PGD2 were converted in HBEC to 9 alpha, 11 beta-PGF2, a potent vasoconstrictor. Exogenous PGD2 also dose-dependently enhanced the production of vasoconstrictive PGF2 alpha, thromboxane B2, vasodilatory prostaglandin PGE2, and cAMP in these cells. The PGD2 stimulated formation of the prostanoids was inhibited by acetylsalicylic acid or indomethacin (inhibitors of cyclooxygenase I) but not dexamethasone, demonstrating for the first time that PGD2 may contribute to the production of prostanoids in HBEC. These findings strongly suggest that PGD2 may play a pivotal role in the regulation of cerebromicrovascular function.