Human astrocytes contain two distinct angiotensin receptor subtypes.
The ability of angiotensin peptides to stimulate prostaglandin release and raise intracellular calcium levels by activating a phosphoinositide-specific phospholipase C was assessed in three human astrocytoma cell lines (CRTG3, STTG1, and WITG2). The addition of angiotensin II to CRTG3 cells resulted in a dose-dependent release of prostaglandin E2 and prostacyclin, the production of inositol 1,4,5-trisphosphate, and the mobilization of intracellular calcium. Angiotensin-(1-7), previously considered to be an inactive metabolite of angiotensin II, was as potent as angiotensin II for prostaglandin release but did not activate phospholipase C or mobilize intracellular calcium. In contrast, angiotensin-(2-8) caused only a slight increase in prostaglandin release, even though it was as effective as angiotensin II in augmenting inositol 1,4,5-trisphosphate production and calcium mobilization. Moreover, neither the release of prostaglandins in response to angiotensin II or angiotensin-(1-7) nor the mobilization of intracellular calcium in response to angiotensin II required extracellular calcium. Angiotensin II and angiotensin-(1-7) caused the release of prostaglandins from all three human astrocytoma cell lines, but changes in the level of intracellular calcium in response to angiotensin II only occurred in CRTG3 cells. Although previous studies have provided evidence for angiotensin receptor subtypes on the basis of selectivity of antagonists or signal transduction mechanisms, these data suggest that human astrocytes contain multiple angiotensin receptor subtypes on the basis of their response to different angiotensin heptapeptides--angiotensin-(1-7) and angiotensin-(2-8).(ABSTRACT TRUNCATED AT 250 WORDS)
Tallant
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Department of Brain and Vascular Research, The Cleveland Clinic Foundation, OH 44195-5286.
Jaiswal
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D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D001253:Astrocytes / Q000737:chemistry*; D001254:Astrocytoma / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003600:Cytosol / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011460:Prostaglandins F / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000096:biosynthesis*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D011460:Prostaglandins F; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III; D015544:Inositol 1,4,5-Trisphosphate; D000803:Angiotensin I; D011464:Epoprostenol; C118790:angiotensin I (1-7); D015232:Dinoprostone; D002118:Calcium; C100006:prostaglandin F1