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. 1988 Dec 1;107(6):2533–2539. doi: 10.1083/jcb.107.6.2533

Intracellular elevations of free calcium induced by activation of histamine H1 receptors in interphase and mitotic HeLa cells: hormone signal transduction is altered during mitosis

PMCID: PMC2115666  PMID: 3204119

Abstract

A broad range of membrane functions, including endocytosis and exocytosis, are strongly inhibited during mitosis. The underlying mechanisms are unclear, however, but will probably be important in relation to the mitotic cycle and the regulation of surface phenomena generally. A major unanswered question is whether membrane signal transduction is altered during mitosis; suppression of an intracellular calcium [( Ca2+]i) transient could inhibit exocytosis; [Ca2+]i elevation could disassemble the mitotic spindle. Activation of the histamine H1 receptor interphase in HeLa cells is shown here by Indo-1 fluorescence to produce a transient elevation of [Ca2+]i. The [Ca2+]i transient consists of an initial sharp rise that is at least partially dependent on intracellular calcium followed by an elevated plateau that is absolutely dependent on extracellular calcium. The [Ca2+]i transient is completely suppressed by preincubation with the tumor promoter, phorbol myristate acetate, but is unaffected by preincubation with pertussis toxin (islet-activating protein). In mitotic (metaphase- arrested) HeLa cells, the [Ca2+]i transient is largely limited to the initial peak. Measurement of 45Ca2+ uptake shows that it is stimulated by histamine in interphase cells, but not in mitotics. We conclude that the histamine-stimulated generation of the second messenger, [Ca2+]i, in mitotic cells is limited by failure to activate a sustained calcium influx. The initial phase of calcium mobilization from intracellular stores is comparable to that in interphase cells. Hormone signal transduction thus appears to be altered during mitosis.

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Selected References

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  1. Berlin R. D., Oliver J. M., Walter R. J. Surface functions during Mitosis I: phagocytosis, pinocytosis and mobility of surface-bound Con A. Cell. 1978 Oct;15(2):327–341. doi: 10.1016/0092-8674(78)90002-8. [DOI] [PubMed] [Google Scholar]
  2. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bielkiewicz-Vollrath B., Carpenter J. R., Schulz R., Cook D. A. Early production of 1,4,5-inositol trisphosphate and 1,3,4,5-inositol tetrakisphosphate by histamine and carbachol in ileal smooth muscle. Mol Pharmacol. 1987 May;31(5):513–522. [PubMed] [Google Scholar]
  4. Cannon C., van Adelsberg J., Kelly S., Al-Awqati Q. Carbon-dioxide-induced exocytotic insertion of H+ pumps in turtle-bladder luminal membrane: role of cell pH and calcium. Nature. 1985 Apr 4;314(6010):443–446. doi: 10.1038/314443a0. [DOI] [PubMed] [Google Scholar]
  5. Di Virgilio F., Meyer B. C., Greenberg S., Silverstein S. C. Fc receptor-mediated phagocytosis occurs in macrophages at exceedingly low cytosolic Ca2+ levels. J Cell Biol. 1988 Mar;106(3):657–666. doi: 10.1083/jcb.106.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. García-Sáinz J. A., de la Garza M. C., Contreras-Rodríguez J. L., Nájera-Alvarado A. Effects of histamine on the metabolism of isolated rat hepatocytes: roles of H1- and H2-histamine receptors. Mol Pharmacol. 1987 Mar;31(3):253–258. [PubMed] [Google Scholar]
  7. Goldman D. W., Chang F. H., Gifford L. A., Goetzl E. J., Bourne H. R. Pertussis toxin inhibition of chemotactic factor-induced calcium mobilization and function in human polymorphonuclear leukocytes. J Exp Med. 1985 Jul 1;162(1):145–156. doi: 10.1084/jem.162.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  9. Hazama A., Yada T., Okada Y. HeLa cells have histamine H1-receptors which mediate activation of the K+ conductance. Biochim Biophys Acta. 1985 May 30;845(2):249–253. doi: 10.1016/0167-4889(85)90183-1. [DOI] [PubMed] [Google Scholar]
  10. Hepler P. K. Calcium restriction prolongs metaphase in dividing Tradescantia stamen hair cells. J Cell Biol. 1985 May;100(5):1363–1368. doi: 10.1083/jcb.100.5.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hesketh T. R., Beaven M. A., Rogers J., Burke B., Warren G. B. Stimulated release of histamine by a rat mast cell line is inhibited during mitosis. J Cell Biol. 1984 Jun;98(6):2250–2254. doi: 10.1083/jcb.98.6.2250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Izant J. G. The role of calcium ions during mitosis. Calcium participates in the anaphase trigger. Chromosoma. 1983;88(1):1–10. doi: 10.1007/BF00329497. [DOI] [PubMed] [Google Scholar]
  13. Katada T., Ui M. ADP ribosylation of the specific membrane protein of C6 cells by islet-activating protein associated with modification of adenylate cyclase activity. J Biol Chem. 1982 Jun 25;257(12):7210–7216. [PubMed] [Google Scholar]
  14. Kuno M., Gardner P. Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes. Nature. 1987 Mar 19;326(6110):301–304. doi: 10.1038/326301a0. [DOI] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Lewis S. A., de Moura J. L. Apical membrane area of rabbit urinary bladder increases by fusion of intracellular vesicles: an electrophysiological study. J Membr Biol. 1984;82(2):123–136. doi: 10.1007/BF01868937. [DOI] [PubMed] [Google Scholar]
  17. Masters S. B., Martin M. W., Harden T. K., Brown J. H. Pertussis toxin does not inhibit muscarinic-receptor-mediated phosphoinositide hydrolysis or calcium mobilization. Biochem J. 1985 May 1;227(3):933–937. doi: 10.1042/bj2270933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matsumoto T., Kanaide H., Nishimura J., Shogakiuchi Y., Kobayashi S., Nakamura M. Histamine activates H1-receptors to induce cytosolic free calcium transients in cultured vascular smooth muscle cells from rat aorta. Biochem Biophys Res Commun. 1986 Feb 26;135(1):172–177. doi: 10.1016/0006-291x(86)90958-7. [DOI] [PubMed] [Google Scholar]
  19. Melmed R. N., Karanian P. J., Berlin R. D. Control of cell volume in the J774 macrophage by microtubule disassembly and cyclic AMP. J Cell Biol. 1981 Sep;90(3):761–768. doi: 10.1083/jcb.90.3.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nakahata N., Martin M. W., Hughes A. R., Hepler J. R., Harden T. K. H1-histamine receptors on human astrocytoma cells. Mol Pharmacol. 1986 Feb;29(2):188–195. [PubMed] [Google Scholar]
  21. Neer E. J., Lok J. M., Wolf L. G. Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase. J Biol Chem. 1984 Nov 25;259(22):14222–14229. [PubMed] [Google Scholar]
  22. Neher E., Almers W. Fast calcium transients in rat peritoneal mast cells are not sufficient to trigger exocytosis. EMBO J. 1986 Jan;5(1):51–53. doi: 10.1002/j.1460-2075.1986.tb04176.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ohsako S., Deguchi T. Receptor-mediated regulation of calcium mobilization and cyclic GMP synthesis in neuroblastoma cells. Biochem Biophys Res Commun. 1984 Jul 18;122(1):333–339. doi: 10.1016/0006-291x(84)90479-0. [DOI] [PubMed] [Google Scholar]
  24. Okajima F., Ui M. ADP-ribosylation of the specific membrane protein by islet-activating protein, pertussis toxin, associated with inhibition of a chemotactic peptide-induced arachidonate release in neutrophils. A possible role of the toxin substrate in Ca2+-mobilizing biosignaling. J Biol Chem. 1984 Nov 25;259(22):13863–13871. [PubMed] [Google Scholar]
  25. Oliver J. M., Seagrave J. C., Pfeiffer J. R., Feibig M. L., Deanin G. G. Surface functions during mitosis in rat basophilic leukemia cells. J Cell Biol. 1985 Dec;101(6):2156–2166. doi: 10.1083/jcb.101.6.2156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ottaviano Y., Gerace L. Phosphorylation of the nuclear lamins during interphase and mitosis. J Biol Chem. 1985 Jan 10;260(1):624–632. [PubMed] [Google Scholar]
  27. Poenie M., Alderton J., Steinhardt R., Tsien R. Calcium rises abruptly and briefly throughout the cell at the onset of anaphase. Science. 1986 Aug 22;233(4766):886–889. doi: 10.1126/science.3755550. [DOI] [PubMed] [Google Scholar]
  28. Preston S. F., Regula C. S., Sager P. R., Pearson C. B., Daniels L. S., Brown P. A., Berlin R. D. Glycosaminoglycan synthesis is depressed during mitosis and elevated during early G1. J Cell Biol. 1985 Sep;101(3):1086–1093. doi: 10.1083/jcb.101.3.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Putney J. W., Jr A model for receptor-regulated calcium entry. Cell Calcium. 1986 Feb;7(1):1–12. doi: 10.1016/0143-4160(86)90026-6. [DOI] [PubMed] [Google Scholar]
  30. Radley J. M., Hodgson G. S. Effect of isoprenaline on cells in different phases of the mitotic cycle. Exp Cell Res. 1971 Nov;69(1):148–160. doi: 10.1016/0014-4827(71)90320-x. [DOI] [PubMed] [Google Scholar]
  31. Ratan R. R., Shelanski M. L., Maxfield F. R. Transition from metaphase to anaphase is accompanied by local changes in cytoplasmic free calcium in Pt K2 kidney epithelial cells. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5136–5140. doi: 10.1073/pnas.83.14.5136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sager P. R., Brown P. A., Berlin R. D. Analysis of transferrin recycling in mitotic and interphase HeLa cells by quantitative fluorescence microscopy. Cell. 1984 Dec;39(2 Pt 1):275–282. doi: 10.1016/0092-8674(84)90005-9. [DOI] [PubMed] [Google Scholar]
  33. Sasaki K., Sato M. A single GTP-binding protein regulates K+-channels coupled with dopamine, histamine and acetylcholine receptors. Nature. 1987 Jan 15;325(6101):259–262. doi: 10.1038/325259a0. [DOI] [PubMed] [Google Scholar]
  34. Sauvé R., Simoneau C., Parent L., Monette R., Roy G. Oscillatory activation of calcium-dependent potassium channels in HeLa cells induced by histamine H1 receptor stimulation: a single-channel study. J Membr Biol. 1987;96(3):199–208. doi: 10.1007/BF01869302. [DOI] [PubMed] [Google Scholar]
  35. Sharkey N. A., Leach K. L., Blumberg P. M. Competitive inhibition by diacylglycerol of specific phorbol ester binding. Proc Natl Acad Sci U S A. 1984 Jan;81(2):607–610. doi: 10.1073/pnas.81.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Steinhardt R. A., Alderton J. Intracellular free calcium rise triggers nuclear envelope breakdown in the sea urchin embryo. Nature. 1988 Mar 24;332(6162):364–366. doi: 10.1038/332364a0. [DOI] [PubMed] [Google Scholar]
  37. Truett A. P., 3rd, Verghese M. W., Dillon S. B., Snyderman R. Calcium influx stimulates a second pathway for sustained diacylglycerol production in leukocytes activated by chemoattractants. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1549–1553. doi: 10.1073/pnas.85.5.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Twigg J., Patel R., Whitaker M. Translational control of InsP3-induced chromatin condensation during the early cell cycles of sea urchin embryos. Nature. 1988 Mar 24;332(6162):366–369. doi: 10.1038/332366a0. [DOI] [PubMed] [Google Scholar]
  39. Warren G., Davoust J., Cockcroft A. Recycling of transferrin receptors in A431 cells is inhibited during mitosis. EMBO J. 1984 Oct;3(10):2217–2225. doi: 10.1002/j.1460-2075.1984.tb02119.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Warren G., Featherstone C., Griffiths G., Burke B. Newly synthesized G protein of vesicular stomatitis virus is not transported to the cell surface during mitosis. J Cell Biol. 1983 Nov;97(5 Pt 1):1623–1628. doi: 10.1083/jcb.97.5.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Westwood J. T., Church R. B., Wagenaar E. B. Changes in protein phosphorylation during the cell cycle of Chinese hamster ovary cells. J Biol Chem. 1985 Aug 25;260(18):10308–10313. [PubMed] [Google Scholar]
  42. Wolniak S. M., Bart K. M. Nifedipine reversibly arrests mitosis in stamen hair cells of tradescantia. Eur J Cell Biol. 1986 Jan;39(2):273–277. [PubMed] [Google Scholar]
  43. Zeilig C. E., Johnson R. A., Sutherland E. W., Friedman D. L. Adenosine 3':5'-monophosphate content and actions in the division cycle of synchronized HeLa cells. J Cell Biol. 1976 Nov;71(2):515–534. doi: 10.1083/jcb.71.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. van Adelsberg J., Al-Awqati Q. Regulation of cell pH by Ca+2-mediated exocytotic insertion of H+-ATPases. J Cell Biol. 1986 May;102(5):1638–1645. doi: 10.1083/jcb.102.5.1638. [DOI] [PMC free article] [PubMed] [Google Scholar]

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