Jaiswal N, Tallant E A, Diz D I, Khosla M C, Ferrario C M
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195-5286.
Hypertension. 1991 Jun;17(6 Pt 2):1115-20. doi: 10.1161/01.hyp.17.6.1115.
We have identified two distinct cellular responses that occur in human astrocytes in the presence of angiotensin (Ang) peptides and are linked to specific receptor subtypes. Ang II and the N-terminal heptapeptide Ang-(1-7) stimulated release of prostaglandin (PG) E2 and PGI2 (measured as the stable metabolite 6-keto-PGF1 alpha). In contrast, only Ang II but not Ang-(1-7) activated phosphoinositide-specific phospholipase C, leading to mobilization of intracellular calcium. The Ang II-induced PGE2 and PGI2 syntheses were attenuated by [Sar1,Ile8]Ang II but not by [Sar1,Thr8]Ang II. Ang-(1-7)-induced PGE2 and PGI2 syntheses were not inhibited by either of these two classical antagonists. DuP 753, a subtype 1-selective Ang receptor antagonist, blocked the Ang II-induced release of PGE2 but not PGI2. In contrast, CGP 42112A, the subtype 2-selective antagonist, totally blocked the Ang II-induced PGI2 release and partially attenuated the PGE2 release. Ang-(1-7)-induced PGE2 and PGI2 release was not altered by DuP 753; however, CGP 42112A totally blocked the effects of Ang-(1-7) on PG stimulation. Calcium mobilization in response to Ang II was blocked by [Sar1,Thr8]Ang II, [Sar1,Ile8]Ang II, and DuP 753 but not by CGP 42112A. These data suggest that human astrocytes contain both Ang receptor subtypes. The subtype 1 Ang receptor participates both in the release of PGs and in the mobilization of calcium, whereas the subtype 2 receptor is coupled to the release of PGs only. In addition, PG release coupled to subtype 2 Ang II receptors occurs through a calcium-independent mechanism and responds uniquely to Ang-(1-7).
我们已经确定了在存在血管紧张素（Ang）肽的情况下人类星形胶质细胞中发生的两种不同的细胞反应，且这些反应与特定的受体亚型相关。血管紧张素II（Ang II）和N端七肽Ang-(1-7)刺激前列腺素（PG）E2和前列环素（PGI2）的释放（以稳定代谢物6-酮-前列腺素F1α衡量）。相比之下，只有Ang II而非Ang-(1-7)激活了磷酸肌醇特异性磷脂酶C，导致细胞内钙的动员。Ang II诱导的PGE2和PGI2合成被[Sar1,Ile8]Ang II减弱，但未被[Sar1,Thr8]Ang II减弱。Ang-(1-7)诱导的PGE2和PGI2合成未被这两种经典拮抗剂中的任何一种抑制。1型选择性Ang受体拮抗剂杜普753（DuP 753）阻断了Ang II诱导的PGE2释放，但未阻断PGI2释放。相比之下，2型选择性拮抗剂CGP 42112A完全阻断了Ang II诱导的PGI2释放，并部分减弱了PGE2释放。Ang-(1-7)诱导的PGE2和PGI2释放未被杜普753改变；然而，CGP 42112A完全阻断了Ang-(1-7)对PG刺激的作用。对Ang II的钙动员被[Sar1,Thr8]Ang II、[Sar1,Ile8]Ang II和杜普753阻断，但未被CGP 42112A阻断。这些数据表明人类星形胶质细胞含有两种Ang受体亚型。1型Ang受体既参与PG的释放，也参与钙的动员，而2型受体仅与PG的释放偶联。此外，与2型Ang II受体偶联的PG释放通过一种不依赖钙的机制发生，并且对Ang-(1-7)有独特反应。
