Spatz M, Stanimirovic D B, Uematsu S, McCarron R M
Stroke Branch, NINDS, NIH, Bethesda, MD 20892.
J Auton Nerv Syst. 1994 Sep;49 Suppl:S123-7. doi: 10.1016/0165-1838(94)90099-x.
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.
前列腺素D2（PGD2）是源自人脑的培养微血管内皮细胞（HBEC）中形成的主要类前列腺素，其他类前列腺素也在其中形成。血管紧张素II、精氨酸加压素和内皮素-1以浓度依赖性方式刺激PGD2和PGF2α的产生，并且这种作用被它们的特异性受体拮抗剂或地塞米松（磷脂酶A2/环氧化酶II抑制剂）所抑制。肽能诱导的PGD2和外源性添加的PGD2在HBEC中均被转化为9α，11β-PGF2，一种强效血管收缩剂。外源性PGD2还以剂量依赖性方式增强了这些细胞中血管收缩性PGF2α、血栓素B2、血管舒张性前列腺素PGE2和环磷酸腺苷（cAMP）的产生。PGD2刺激的类前列腺素形成被乙酰水杨酸或吲哚美辛（环氧化酶I抑制剂）抑制，但不被地塞米松抑制，首次证明PGD2可能有助于HBEC中类前列腺素的产生。这些发现强烈表明PGD2可能在脑微血管功能调节中起关键作用。
