Angiotensin II causes phosphatidylinositol turnover and increases 1,2-diacylglycerol mass but is not mitogenic in rat liver T51B cells.
Proliferation in rat liver T51B cells has previously been shown to be initiated by the tyrosine-kinase activator epidermal growth factor. We have found that T51B cells also contain angiotensin II receptors, and, as the transforming mas oncogene has been identified as a functional angiotensin receptor [Jackson, Blair, Marshall, Goedert & Hanley (1988) Nature (London) 335, 437-440], we have investigated the possibility that angiotensin II might also regulate proliferation of T51B cells. Angiotensin II at concentrations up to 10 microM did not promote DNA synthesis, even in the presence of the co-mitogens serum (1%) or 12-O-tetradecanoylphorbol 13-acetate (TPA) (50 ng/ml). The addition of 1 microM angiotensin II to myo-[3H]inositol-radiolabelled T51B cells did however result in a rapid accumulation of multiple inositol phosphates as well as in an increase in intracellular Ca2+, demonstrating the coupling of the angiotensin receptor in these cells to a polyphosphoinositide-hydrolysing phospholipase C. The increases in both inositol phosphates and intracellular Ca2+ were lower in cells pretreated for 10 min with 50 ng of TPA/ml and potentiated by a 24 h pretreatment with TPA. In addition, angiotensin II increased 1,2-diacylglycerol levels. These results demonstrate that, although angiotensin II is capable of increasing phosphoinositide-derived second messengers in T51B cells, these responses are not sufficient to trigger DNA synthesis.
Dean
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Basic Science Program, Cancer Research Center, University of Hawaii, Honolulu 96813.
Boynton
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D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004075:Diglycerides / Q000378:metabolism*; D015536:Down-Regulation; D005989:Glycerides / Q000378:metabolism*; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C011439:1,2-diacylglycerol; D004075:Diglycerides; D005989:Glycerides; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D000804:Angiotensin II; D007294:Inositol; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium