title: Subtype 2 angiotensin receptors mediate prostaglandin synthesis in human astrocytes.
abstract: 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).
authors.affiliation: Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195-5286.
authors.forename: N
authors.initials: N
authors.lastname: Jaiswal
authors.forename: E A
authors.initials: EA
authors.lastname: Tallant
authors.forename: D I
authors.initials: DI
authors.lastname: Diz
authors.forename: M C
authors.initials: MC
authors.lastname: Khosla
authors.forename: C M
authors.initials: CM
authors.lastname: Ferrario
mesh_terms: D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D011453:Prostaglandins / Q000096:biosynthesis*; D011945:Receptors, Angiotensin / Q000502:physiology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D011453:Prostaglandins; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D002118:Calcium