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Role of Ca2+-ATPases in regulation of cellular Ca2+ signalling, as studied with the selective microsomal Ca2+-ATPase inhibitor, thapsigargin

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References

  1. E. Carafoli,Intracellular calcium homeostasis. Ann. Rev. Biochem.56, 395–433 (1987).

    PubMed  Google Scholar 

  2. F. Wuytack, L. Raeymaekers, J. Verbist and R. Casteels,Ca 2+-transport ATPases in the plasma membrane and endoplasmic reticulum. InThe role of calcium in biological systems. (Ed. L. J. Anghileri) pp. 115–162, CRC press, Boca Raton 1987.

    Google Scholar 

  3. E. Carafoli,The transport of calcium across the inner membrane of mitochondria. InMembrane transport of calcium. (Ed. E. Carafoli) pp. 109–139, Academic press, London 1982.

    Google Scholar 

  4. J. T. Penniston, InCalcium and cells function. Vol. 4 (Ed. W. Y. Cheung), pp. 99–149, Academic Press, New York 1983.

    Google Scholar 

  5. P. A. Knauf, F. Proverbio and J. F. Hoffman,Electrophoretic separation of different phosphoproteins associated with Ca-ATPase and Na, K-ATPase in human red cell ghosts. J. Gen. Physiol.63, 324–336 (1974).

    PubMed  Google Scholar 

  6. P. Caroni and E. Carafoli,The Ca 2+-pumping ATPase of heart sarcolemma. Characterization, calmodulin dependence, and partial purification J. Biol. Chem.256, 3263–3270 (1981).

    PubMed  Google Scholar 

  7. K. I. Furakawa and H. Nakamura,Cyclic GMP regulation of the plasma membrane Ca-Mg ATPase in vascular smooth muscle. J. Biochem.101, 287–290 (1987).

    PubMed  Google Scholar 

  8. H. Schatzmann,The calcium pump of erythrocytes and other animal cells. InMembrane transport of calcium (Ed. E. Carafoli) pp. 41–108, Academic Press, London 1982.

    Google Scholar 

  9. A. K. Verma, A. Filoteo, D. R., Stanford, E. D. Wieben, J. T. Penniston, E. E. Strehler, R. Fischer, R. Heim, G. Vogel, S. Matthews, M.-A. Strehler-Page, P. James, T. Vorherr, J. Krebs and E. Carafoli,Complete primary structure of a human plasma membrane calcium pump. J. biol. Chem.263, 14152–14159 (1988).

    PubMed  Google Scholar 

  10. D. H. MacLennan,Purification and properties of an adenosine triphosphatase from sarcoplasmic reticulum. J. Biol. Chem.245, 4508–4518 (1970).

    PubMed  Google Scholar 

  11. M. Makinose,The phosphorylation of the membranal protein of the sarcoplasmic vesicles during active calcium transport. Eur. J. Biochem.10, 74–82 (1969).

    PubMed  Google Scholar 

  12. M. Worsfold and J. B. Peter,Kinetics of calcium transport by fragmented sarcoplasmic reticulum. J. Biol. Chem.245, 5545–5552 (1970).

    PubMed  Google Scholar 

  13. C. J. Brandl, N. M. Green, B. Korczak and D. H. MacLennan,Two Ca 2+ ATP genes: homologies and mechanistic implications of deduced amino acid sequence. Cell44, 597–607 (1986).

    PubMed  Google Scholar 

  14. B. Korczak, A. Zarain-Herzberg, C. J. Brandl, C. J. Ingles, N. M. Green and D. H. MacLennan,Structure of the rabbit fast twich skeletal muscle Ca 2+-ATPase gene. J. Biol. Chem.263, 4813–4819 (1988).

    PubMed  Google Scholar 

  15. A. J. Caride, J. P. Gorski and J. T. Penniston,Topology of the erythrocyte Ca 2+ pump. A monoclonal antibody against the almost inaccessible extracellular face. Biochem. J.,255, 633–670 (1988).

    Google Scholar 

  16. A. K. Verma, J. T. Penniston, S. Muallem and V. Lew,Effects of affinity-purified antibodies on the Ca 2+ pumping ATPase of erythrocyte membranes. J. Bioenerg. Biomembr.16, 365–378 (1984).

    PubMed  Google Scholar 

  17. D. H. MacLennan, C. J. Brandl, B. Korczak and N. M. Green,Amino-acid sequence of a Ca 2++Mg 2+-dependent ATPase from rabbit muscle sarcoplasmic reticulum, deduced from its complementary DNA sequence. Nature316, 696–700 (1985).

    PubMed  Google Scholar 

  18. J. Lytton and D. H. MacLennan,Molecular cloning of cDNAs from human kidney coding for two alternatively spliced products of the cardiac Ca 2+-ATPase gene. J. Biol. Chem.263, 15024–15031 (1988).

    PubMed  Google Scholar 

  19. U. Rasmussen, S. B. Christensen and F. Sandberg,Thapsigargin and thapsigargicin, two new histamine liberators from thapsia garganica. Acta. Pharmaceut. Suec.15, 133–140 (1978).

    Google Scholar 

  20. T. R. Jackson, S. I. Patterson, O., Thastrup and M. R. Hanley,A novel tumour promoter, thapsigargin, transiently increases cytoplasmic free Ca 2+ without generation of inositol phosphates in NG115-401L neuronal cells. Biochem. J.253, 81–86 (1988).

    PubMed  Google Scholar 

  21. H. Hakii, H. Fujiki, M. Suganuma, M. Nakayasu, T. Tahira, T. Sugimura, P. J. Scheuer and S. B. Christensen,Thapsigargin, a histamine secretagogue, is a non-12-O-tetradecanoylphorbol-13-acetate (TPA) type tumor promoter in two-stage mouse skin carcinogenesis. J. Cancer Res. Clin. Oncol.111, 177–181 (1986).

    PubMed  Google Scholar 

  22. O. Thastrup, P. J. Cullen, B. K. Drøbak, M. R. Hanley and A. P. Dawson,Thapsigargin has a novel mechanism of action amongst tumour promoters: discharge of intracellular Ca 2+ stores by specific inhibition of the endoplasmic reticulum-Ca 2+-ATPase (submitted).

  23. O. Thastrup, A. P. Dawson, O. Scharff, B. Foder, P. J. Cullen, B. K. Drøbak, P. J. Bjerrum, S. B. Christensen and M. R. Hanley,Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage. Agents and Actions27, 17–23 (1989).

    PubMed  Google Scholar 

  24. M. D. Nielsen, N. Borregaard and O. Thastrup,A subfraction of the thrombin dischargeable intracellular Ca 2+-pool in human platelets is insensitive to inositol 1,4,5-trisphosphate. Studies with the selective endoplasmic reticulum Ca 2+-ATPase inhibitor, thapsigargin (submitted).

  25. H. Takemura, A. R. Hughes, O. Thastrup and J. W. Putney Jr.,Activation of calcium entry by the tumor promoter, thapsigargin, in parotid acinar cells. Evidence that an intracellular calcium pool, and not an inositol phosphate, regulates calcium fluxes at the plasma membrane. J. Biol. Chem.264, 12266–12271 (1989).

    PubMed  Google Scholar 

  26. W. Jy and D. H. Haynes,Thrombin-induced calcium movements in platelet activation. Biochim. Biophys. Acta929, 88–102 (1987).

    PubMed  Google Scholar 

  27. T. R. Cheek, R. B. Moreton, M. J. Berridge and O. Thastrup,Effects of the Ca 2+-mobilizing tumour promoter thapsigargin and an inositol trisphosphate mobilizing agonist on cystosolic Ca 2+ in bovine adrenal chromaffin cells. Biochem. Soc. Trans.17, 94–95 (1988).

    Google Scholar 

  28. H. P. Benton, T. R. Jackson and M. R. Hanley,Identification of a novel inflammatory stimulant of chondrocytes. Early events in cell activation, by bradykinin receptors on pig articular chondrocytes. Biochem. J.258, 861–867 (1989).

    PubMed  Google Scholar 

  29. R. F. Irvine and R. M. Moor,Micro-injection of inositol(1,3,4,5) tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca 2+. Biochem. J.240, 917–920 (1986).

    PubMed  Google Scholar 

  30. V. von Tscharner, B. Prod'hom, M. Baggiolini and H. Reuter,Ion channels in human neutrophils activated by a rise in free cytosolic calcium concentration. Nature324, 369–372 (1986).

    PubMed  Google Scholar 

  31. R. F. Irvine, R. M. Moor, W. K. Pollock, P. M. Smith and K. A. Wreggett,Inositol phosphates: proliferation, metabolism and function. Phil. Trans. R. Soc. Lond. B.320, 281–297 (1988).

    Google Scholar 

  32. J. W. Putney Jr.,A model for receptor-regulated calcium entry. Cell Calcium7, 1–12 (1986).

    PubMed  Google Scholar 

  33. S. H. Marier, J. W. Putney Jr. and C. M. van de Walle,Control of calcium channels by membrane receptors in the rat parotid gland. J. Physiol., (Lond.)279, 141–151 (1978).

    Google Scholar 

  34. B. Foder, O. Scharff and O. Thastrup,Ca 2+ transients and Mn 2+ uptake in human neutrophils induced by thapsigargin. Cell Calcium (in press).

  35. T. J. Hallam and T. J. Rink,Agonists stimulate divalent cation channels in the plasma membrane of human platelets. FEBS Lett.186, 175–179 (1985).

    PubMed  Google Scholar 

  36. O. Thastrup, B. Foder and O. Scharff,The calcium mobilizing and tumour promoting agent, thapsigargin, elevates the platelet cytoplasmic free calcium concentration to a higher steady state level. A possible mechanism of action for the tumour promotion. Biochem. Biophys. Res. Commun.142, 654–660 (1987).

    PubMed  Google Scholar 

  37. O. Thastrup, H. Linnebjerg, P. J. Bjerrum, J. B. Knudsen and S. B. Christensen,The inflammatory and tumor-promoting sesquiterpene lactone thapsigargin activates platelets by selective mobilization of calcium as shown by protein phosphorylation. Biochem. Biophys. Acta927, 65–73 (1987).

    PubMed  Google Scholar 

  38. O. Scharff, B. Foder, O. Thastrup, B. Hofmann, J. Møller, L. P. Ryder, K. D. Jacobsen, F. Langhoff, E. Dickmeiss, S. Brøgger Christensen, P. Skinhøj and A. Svejgaard,Effect of thapsigargin on cytoplasmic Ca 2+ and proliferation of human lymphocytes in relation to AIDS. Biochim. Biophys. Acta.972, 257–264 (1988).

    PubMed  Google Scholar 

  39. K. Ohuchi, T. Sugawara, M. Watanabe, N. Hirasawa, S. Tsurrufuji, H. Fujiki, S. B. Christensen and T. Sugimura,Analysis of the stimulative effect of thapsigargin, a non-TPA-type tumour promoter, on arachidonic acid metabolism in rat peritoneal macrophages. Br. J. Pharmacol.94, 917–923 (1988).

    PubMed  Google Scholar 

  40. D. J. Brayden, M. R. Hanley, O. Thastrup and A. W. Cuthbert,Thapsigargin, a new calcium dependent epithelial anion secretagogue. Br. J. Pharmacol.98, 809–816 (1989).

    PubMed  Google Scholar 

  41. R. M. Gopinath and F. F. Vincenzi,Phosphodiesterase protein activator mimics red blood cell cytoplasmic activator of (Ca 2+−Mg2+)ATPase. Biochem. Biophys. Res. Commun.77, 1203–1209 (1977).

    PubMed  Google Scholar 

  42. H. W. Jarrett and J. T. Penniston,Partial purification of the Ca 2+Mg 2+-ATPase activator from human erythrocytes: its similarity to the activator of 3′: 5′-cyclic nucleotide phosphodiesterase. Biochem. Biophys. Res. Commun.77, 1210–1216 (1977).

    PubMed  Google Scholar 

  43. V. Niggli, E. S. Adunyah and E. Carafoli,Acidic phospholipids, unsaturated fatty acids, and limited proteolysis mimic the effect of calmodulin on the purified erythrocyte Ca 2+-ATPase. J. Biol. Chem.256, 8588–8592 (1981).

    PubMed  Google Scholar 

  44. L. Neyses, L. Reinlib and E. Carafoli,Phosphorylation of the Ca 2+-pumping ATPase of heart sarcolemma and erythrocyte plasma membrane by the cAMP-dependent protein kinase. J. Biol. Chem.260, 10283–10287, (1985).

    PubMed  Google Scholar 

  45. P. Caroni and E. Carafoli,Regulation of Ca 2+-pumping ATPase of heart sarcolemma by a phosphorylation-dephosphorylation process. J. Biol. Chem.256, 9371–9373 (1981).

    PubMed  Google Scholar 

  46. K. I. Furakawa and H. Nakamura,Cyclic GMP regulation of the plasma membrane Ca−Mg ATPase in vascular smooth muscle. J. Biochem.101, 287–290 (1987).

    PubMed  Google Scholar 

  47. E. Suematsu, M. Hirata and H. Kuriyama,Effects of cyclic AMP-dependent and cyclic-GMP-dependent protein kinases. and calmodulin on calcium uptake by highly purified sarcolemmal vesicles of vascular smooth muscle. Biochem. Biophys. Acta773, 83–90 (1984).

    PubMed  Google Scholar 

  48. P. J. Davis, F. B. Davis and S. D. Blas,Studies on the mechanism of thyroid hormone stimulation in vitro of human red cell Ca 2+-ATPase activity. Life Sci.30, 675–681 (1982).

    PubMed  Google Scholar 

  49. T. H. Kuo,Guanine nucleotide-, and inositol trisphosphate-induced inhibition of the Ca 2+ pump in rat sarcolemmal vesicles. Biochem. Biophys. Res. Commun.152, 1111–1116 (1988).

    PubMed  Google Scholar 

  50. L. M. Popescu, M. E. Hinescu, S. Musat, M. Ionescu and F. Pistritzu,Inositol trisphosphate and the contraction of vascular smooth muscle cells. Eur. J. Pharmacol.123, 167–169 (1986).

    PubMed  Google Scholar 

  51. L. Missiaen, Y. Kanmura, F. Wuytack and R. Casteels,Carbachol partially inhibits the plasma-membrane Ca 2+-pump in microsomes from pig stomach smooth muscle. Biochem. Biophys. Res. Commun.150, 681–686 (1988).

    PubMed  Google Scholar 

  52. I. S. Ambudkar and B. J. Baum,ATP-dependent calcium transport in rat parotid basolateral membrane vesicles in modulated by membrane potential. J. Membr. Biol.102, 59–69 (1989).

    Google Scholar 

  53. V. Prpic, K. C. Green, P. F. Blackmore and J. H. Exton,Vasopressin-, angiotensin II-, and α 1 inhibition of Ca 2+ transport by rat liver plasma membrane vesicles. J. Biol. Chem.259, 1382–1385 (1984).

    PubMed  Google Scholar 

  54. S. Lotersztajn, R. M. Epand, A. Mallat and F. Pecker,Inhibition by glucagon of the calcium pump in liver plasma membranes. J. Biol. Chem.259, 8195–8201 (1984).

    PubMed  Google Scholar 

  55. M. Tada and A. M. Katz,Phosphorylation of the sarcoplasmic reticulum and sarcolemma. Ann. Rev. Physiol.44, 401–423 (1982).

    Google Scholar 

  56. M. A. Kirchberger and M. Tada,Effects of adenosine 3′: 5′-monophosphate-dependent protein kinase on sarcoplasmic reticulum isolated from cardiac and slow and fast contracting skeletal muscles. J. Biol. Chem.251, 725–729 (1976).

    Google Scholar 

  57. J. A. Eggermont, M. Vrolix, L. Racymackers, F. Wuytack and R. Casteels,Ca 2+-transport ATPases of vascular smooth muscle. Circ. Res.62, 266–278 (1988).

    PubMed  Google Scholar 

  58. L. Racymaekers and L. R. Jones,Evidence for the presence of phospholamban in the endoplasmic reticulum of smooth muscle. Biochim. Biophys. Acta882, 258–265 (1986).

    PubMed  Google Scholar 

  59. L. Racymaekers, F. Hofmann and R. Casteels,Stimulation of the Ca 2+ pump of the endoplasmic reticulum of smooth muscle by cyclic nucleotide-dependent protein kinase. J. Muscl. Res. Cell Motility (in press, 1988).

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Thastrup, O. Role of Ca2+-ATPases in regulation of cellular Ca2+ signalling, as studied with the selective microsomal Ca2+-ATPase inhibitor, thapsigargin. Agents and Actions 29, 8–15 (1990). https://doi.org/10.1007/BF01964706

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