Advertisement

Cardiac Effects of AII

AT1A Receptor Signaling, Desensitization, and Internalization
  • W. G. Thomas
  • T. J. Thekkumkara
  • K. M. Baker
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 396)

Summary

Angiotensin II receptors present in cardiomyocytes, nonmyocytes (predominantly fibroblasts), nerve terminals, and the heart vasculature mediate the multiple actions of angiotensin II (AII) in the heart, including modulation of normal and patho-physiological cardiac growth. Although the cellular processes that couple AII receptors (principally the AT1 subtype) to effector responses are not completely understood, recent studies have identified an array of signal transduction pathways activated by AII in cardiac cells. These include: the stimulation of phospholipase C which results in the activation of protein kinase C and the release of calcium from intracellular stores; an enhancement of phosphaditic acid formation; the coupling to soluble tyrosine kinase phosphorylation events; the initiation of the mitogen activated protein kinase (MAPK) cascade; and the induction of the STAT (Signal Transducers and Activators of Transcription) signaling pathway. It is tempting to speculate that these latter responses, which have been previously associated with growth factor signaling pathways, are involved in AII-induced cardiac growth. Interestingly, some of these novel pathways are apparently not under the same strict control imposed upon the more classical signaling pathways. Thus, while AII-induced calcium transients are rapidly (within minutes) desensitized following exposure to AII, the MAP kinase pathway is not, and activation of the STAT pathway requires hours of agonist exposure for maximal induction. These observations support an emerging picture in which the downstream signal transduction pathways of AII receptors are initiated and terminated with a distinct temporal arrangement. This organization allows appropriate rapid responses (e.g. vascular contraction) to transient AII exposure, some of which are rapidly terminated, perhaps for protective reasons, and others not. In contrast, additional responses (e.g. growth) probably require prolonged exposure to agonist.

Keywords

Mitogen Activate Protein Kinase Tyrosine Phosphorylation Cardiac Fibroblast Calcium Transient Stat Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Morgan, H.E., and Baker, K.M. (1991). Circulation 83: 13–25.PubMedCrossRefGoogle Scholar
  2. 2.
    Baker, K.M., Booz, G.W., and Dostal, D.E. (1992). Annu. Rev. Physiol. 54: 227–241.PubMedCrossRefGoogle Scholar
  3. 3.
    Booz, G.W., Dostal, D.E., and Baker, K.M. (1994), in The Cardiac Renin Angiotensin System (eds. K. Lindpainter, D. Ganten), Futura, NY, pp 101–123.Google Scholar
  4. 4.
    Rogers, T.B., and Lokuta, A.J. (1994). Trends Cardiovasc. Med. 4: 100–116.CrossRefGoogle Scholar
  5. 5.
    Dostal, D.E., and Baker, K.M. (1993). Trends Cardiovasc. Med. 3: 67–74.PubMedCrossRefGoogle Scholar
  6. 6.
    Dostal, D.E., Baker, K.M., and Peach, M.J. (1991), in Horizons in Endocrinology (eds. M. Maggi, V. Greenen), Raven Press, NY, 76: 265–272.Google Scholar
  7. 7.
    Dostal, D.E., Booz, G.W., and Baker, K.M. (1994), in The Cardiac Renin Angiotensin System (eds. K. Lindpainter, D. Ganten), Futura, NY, pp 1–20.Google Scholar
  8. 8.
    Paul, M., Wagner, J., and Dzau, V.J. (1993). J. Clin. Invest. 91: 2058–2064.PubMedCrossRefGoogle Scholar
  9. 9.
    Dostal, D.E., Rothblum, K.C., Chemin, M.I., Copper, G.R., and Baker, K.M. (1992). Am. J. Physiol. 263: C838–863.PubMedGoogle Scholar
  10. 10.
    Dostal, D.E., Rothblum, K.C., Conrad, K.M., Cooper, G.R., Baker, K.M. (1992). Am. J. Physiol. 263: C851–C863.PubMedGoogle Scholar
  11. 11.
    Sadoshima, J., Xu, Y., Slayter, H.S., and Izumo, S. (1993). Cell 75: 977–984.PubMedCrossRefGoogle Scholar
  12. 12.
    Baker, K.M., Chemin, M.I., Wixson, S.K., and Aceto, J.F. (1990). Am. J. Physiol. 259: H324–332.PubMedGoogle Scholar
  13. 13.
    Everett, A.D., Tufro-McReddie, A., Fisher, A., and Gomez, R.A. (1994). Hypertension 23: 587–592.PubMedCrossRefGoogle Scholar
  14. 14.
    Bruckschlegel, G., Holmer, S.R., Jandeleit, K., Grimm, D., Muders, F., Kromer, E.P., Riegger, G.A.J., and Schunkert, H. (1995). Hypertension 25: 250–259.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhou, J., Allen, A.M., Yamada, H., Sun, Y., and Mendelsohn, F.A.O. (1994), in The Cardiac Renin Angiotensin System (eds. K. Lindpainter, D. Ganten), Futura, NY, pp 63–88.Google Scholar
  16. 16.
    Meggs, L.G., Coupet, J., Huang, H., Li, W.C.P., Capasso, J.M., Homey, C.J., and Anversa, P. (1993). Circ. Res. 72: 1149–1162.PubMedCrossRefGoogle Scholar
  17. 17.
    Nio, Y., Matsubara, H., Murasawa, S., Kanasaki, M., and Inada, M. (1995). J. Clin. Invest. 95: 46–54.PubMedCrossRefGoogle Scholar
  18. 18.
    Suzuki, J., Matsubara, H., Urakami, M., and Inada, M. (1993). Circ. Res. 73: 439–447.PubMedCrossRefGoogle Scholar
  19. 19.
    Regitz-Zagrosek, V., Friedel, N., Heymann, A., Bauer, P., Neuss, M., Rolfs, A., Steffen, C., Hildebrandt, A., Hetzer, R., and Fleck, E. (1995). Circulation 91: 1461–1471.PubMedCrossRefGoogle Scholar
  20. 20.
    Inagami, T., Iwai, N., Sasaki, K., Guo, D.F., Furata, H., Yamano, Y., Bardhan, S., Chaki, S., Makito, N., and Badr, K. (1993). Drug Res. 43: 226–228.Google Scholar
  21. 21.
    Shanmugan, S., Corvol, P., and Gasc, J. (1994). Am. J. Physiol. 267: E828–836.Google Scholar
  22. 22.
    Grady, E.F., Sechi, L.A., Griffin, C.A., Schambelan, M., and Kalinyak, J.E. (1991). J. Clin. Invest. 88: 921–933.PubMedCrossRefGoogle Scholar
  23. 23.
    Buisson, B., Laflamme, L., Bottari, S.P., De Gasparo, M., Gallo-Payet, N., and Payet, M.D. (1995). J. Biol. Chem. 270: 1670–1674.PubMedCrossRefGoogle Scholar
  24. 24.
    Nahmias, C., Cazaubon, S.M., Briend-Sutren, M.M., Lazard, D., Villgeios, P., and Strosberg, A.D. (1995). Biochem. J. 306: 87–92.PubMedGoogle Scholar
  25. 25.
    Tanaka, M., Ohnishi, J., Ozawa, Y., Sugimoto, M., Usuki, S., Naruse, M., Murakami, K., and Miyazaki, H. (1995). Biochem. Biophys. Res. Commun. 207: 593–598.PubMedCrossRefGoogle Scholar
  26. 26.
    Stoll, M., Steckelings, M., Paul, M., Bottari, S.P., Metzger, R., and Unger, T. (1995). J. Clin. Invest. 95: 651–657.PubMedCrossRefGoogle Scholar
  27. 27.
    Baker, K.M., Singer, H.A., and Aceto, J.F. (1989). J. Pharmacol. Exp. Ther. 251: 578–585.PubMedGoogle Scholar
  28. 28.
    Aceto, J.F., and Baker, K.M. (1990). Am. J. Physiol. 258: H806–813.PubMedGoogle Scholar
  29. 29.
    Baker, K.M., and Aceto, J.F. (1990). Am. J. Physiol. 259: H610–618.PubMedGoogle Scholar
  30. 30.
    Sadoshima, J., and Izumo, S. (1993). Circ. Res. 73: 413–423.PubMedCrossRefGoogle Scholar
  31. 31.
    Schorb, W., Booz, G.W., Dostal, D.E., Chang, K.C., and Baker, K.M. (1993). Circ. Res. 72: 1245–1254.PubMedCrossRefGoogle Scholar
  32. 32.
    Schorb, W., Conrad, K.C., Singer, H.A., Dostal, D.E., and Baker, K.M. J. Mol. Cell. Cardiol. (in press).Google Scholar
  33. 33.
    Booz, G.W., Dostal, D.E., Singer, H.A., and Baker, K.M. (1994). Am. J. Physiol. 267: C1308–1318.PubMedGoogle Scholar
  34. 34.
    Booz, G.W., and Baker, K.M. Cardiovasc. Res. (in press).Google Scholar
  35. 35.
    Sadoshima, J., and Izumo, S. (1993). Circ. Res. 73: 424–438.PubMedCrossRefGoogle Scholar
  36. 36.
    Booz, G.W., Taher, M.M., Baker, K.M., and Singer, H.A. (1994). Mol. Cell. Biochem. 141: 135–143.PubMedCrossRefGoogle Scholar
  37. 37.
    Thomas, W.G., Thekkumkara, T.J., Motel, T.J., and Baker, K.M. (1995). J. Biol. Chem. 270: 207–213.PubMedCrossRefGoogle Scholar
  38. 38.
    Inui, H., Kondo, T., Konishi, F., Kitami, Y., and Inagami, T. (1994). Biochem. Biophys. Res. Commun. 205: 1338–1344.PubMedCrossRefGoogle Scholar
  39. 39.
    Schorb, W., Peeler, T.C., Madigan, N.N., Conrad, K.M., and Baker, K.M. (1994). J. Biol. Chem. 269: 19626–19632.PubMedGoogle Scholar
  40. 40.
    Leduc, I., and Meloche, S. (1995). J. Biol. Chem. 270: 4401–4404.PubMedCrossRefGoogle Scholar
  41. 41.
    Darnell, J.E., Kerr, I.M., and Stark, G.R. (1994). Science 264: 1415–1421.PubMedCrossRefGoogle Scholar
  42. 42.
    Stahl, N., Farruggella, T.J., Boulton, T.G., Zhong, Z., Darnell, J.E., and Yancopoulos, G.D. (1995). Science 267: 1349–1353.PubMedCrossRefGoogle Scholar
  43. 43.
    Bhat, G.J., Thekkumkara, T.J., Thomas, W.G., Conrad, K.C., and Baker, K.M. (1994). J. Biol. Chem. 269: 31443–31449.PubMedGoogle Scholar
  44. 44.
    Sasamura, H., Dzau, V.J., and Pratt, R.E. (1994). Kidney Int. 46: 1499–1501.PubMedCrossRefGoogle Scholar
  45. 45.
    Thekkumkara, T.J., Du, J., Dostal, D.E., Motel, T.J., Thomas, W.G., and Baker, K.M. Mol. Cell. Biochem. (in press).Google Scholar
  46. 46.
    Premont, R.T., Inglese, J., Lefkowitz, R.J. (1995). FASEB J. 9: 175–182.PubMedGoogle Scholar
  47. 47.
    Paxton, W.G., Marrero, M.B., Klein, J.D., Delafontaine, P., Berk, B.C., and Bernstein, K.E. (1994). Biochem. Biophys. Res. Commun. 200: 260–267.PubMedCrossRefGoogle Scholar
  48. 48.
    Kai, H., Griendling, K.K., Lassegue, B., Ollerenshaw, J.D., Runge, M.S., and Alexander, R.W. (1994). Hypertension 24: 523–521.PubMedCrossRefGoogle Scholar
  49. 49.
    Boulay, G., Chretien, L., Richard, D.E., and Guillemette, G. (1994). Endocrinology 135: 2130–2136.PubMedCrossRefGoogle Scholar
  50. 50.
    Roberston, M.J., Dougall, LG., Harper, D., McKechnie, K.C.W., and Leff, P. (1994). Trends Pharmacol. Sci. 15: 364–369.CrossRefGoogle Scholar
  51. 51.
    Rui, H., Lebrun, J.J., Kirken, R.A., Kelly, P.A., and Farrar, W.L. (1994). Endocrinology 135: 1299–1306.PubMedCrossRefGoogle Scholar
  52. 52.
    Miyamoto, S., Akiyama, S.K., and Yamada, K.M. (1995). Science 267: 883–885.PubMedCrossRefGoogle Scholar
  53. 53.
    Kapas, S., Hinson, J.P., Puddefoot, J.R., Ho, M.M., and Vinson, G.P. (1994). Biochem. Biophys. Res. Commun. 204: 1292–1298.PubMedCrossRefGoogle Scholar
  54. 54.
    Conchon, S., Monnot, C., Teutsch, B., Corvol, P., and Clauser, E. (1994). FEBS Lett. 349: 365–310.PubMedCrossRefGoogle Scholar
  55. 55.
    Hunyday, L., Bor, M., Balla, T., and Catt, K.J. (1994). J.Biol. Chem. 50: 31378–31382.Google Scholar
  56. 56.
    Hunyday, L., Baukal, A.J., Balla, T., and Catt, K.J. (1994). J. Biol. Chem. 40: 24798–24804.Google Scholar
  57. 57.
    Pearse, B.M.F., and Robinson, M.S. (1990). Annu. Rev. Cell. Biol. 6: 151–171.PubMedCrossRefGoogle Scholar
  58. 58.
    Trowbridge, L.S., Collawn, J.F., and Hopkins, C.R. (1993). Annu. Rev. Cell. Biol. 9: 129–161.PubMedCrossRefGoogle Scholar
  59. 59.
    Chaki, S., Guo, D., Yamano, Y., Ohyama, K., Tani, M., Mizukoshi, M., Shirai, H., and Inagami, T. (1994). Kidney Int. 46: 1492–1495.PubMedCrossRefGoogle Scholar
  60. 60.
    Rohrer, J., Benedetti, H., Zanolari, B., and Riezman, H. (1993). Mol. Biol. Cell 4: 511–521.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • W. G. Thomas
    • 1
  • T. J. Thekkumkara
    • 1
  • K. M. Baker
    • 1
  1. 1.Weis Center for ResearchGeisinger ClinicDanvilleUSA

Personalised recommendations