Peptide Hormones, Cytosolic Calcium and Renal Epithelial Response

  • Aubrey R. Morrison
  • Didier Portilla
  • Daniel Coyne
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 259)


The response of renal cells to extracellular signals has recently attracted increasing experimental evaluation. The cellular response to a variety of peptide hormones, neurotransmitters and growth factors are fundamental to understanding how the signals mediated by circulatory substances, which interact with cell surface receptors, produce their effects intracellularly. The cellular responses to a wide variety of signal molecules are somewhat limited. Occupancy of receptors initiates the production of intracellular messengers including cAMP, cGMP and the second messenger molecules derived from phosphoinositides (1–3). The phosphoinositides constitute 5–8% of lipids in the cell membranes of eukaryotic cells and are essential for cell viability (4). These phosphoinositides are storage forms for the messenger molecules that transmit signals across the cell membrane and evoke responses to extracellular signals.


Parathyroid Hormone MDCK Cell Tubule Cell Calcium Transient Lithium Chloride 


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  1. 1.
    Y. Nishizuka, Studies and perspectives of protein kinase C, Science 233:305–312 (1986).PubMedCrossRefGoogle Scholar
  2. 2.
    M.J. Berridge and R.F. Irvine, Inositol trisphosphate, a novel second messenger in signal transduction, Nature (London) 312:315–321 (1984).CrossRefGoogle Scholar
  3. 3.
    P.N. Majerus, T.M. Connolly, H. Deckmyer, T.S. Ross, T.E. Bross, H. Ishii, V.S. Bansal, D.B. Wilson, The metabolism of phosphoinositide-derived messenger molecule, Science 234:1519–1526 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    J. Esko and C.R.H. Raetz, Mutants of Chinese hamster ovary cells with altered membrane phospholipid composition, J. Biol. Chem. 255:4474–4480 (1980).PubMedGoogle Scholar
  5. 5.
    S. Shin, Y. Fujiwara, A. Wada, T. Takama, Y. Orita, T. Kamada, K. Tagawa, Angiotensin II-induced increase in inositol 1, 4, 5-trisphosphate in cultured rat mesangial cells: evidence by refined High Performance Liquid Chromatography, BBRC 142:70–77 (1987).PubMedGoogle Scholar
  6. 6.
    J.E. Benabe, L.A. Spry, A.R. Morrison, Effects of angiotensin II on phosphatidylinositol and polyphosphatidylinositol turnover in rat kidney, J. Mol. Chem. 257:7430–7434 (1982).Google Scholar
  7. 7.
    J.A. Shayman and A.R. Morrison, Bradykinin-induced changes in phosphatidylinositol turnover in cultured rabbit papillary collecting tubule cells, J. Clin. Invest. 76:978–984 (1985).PubMedCrossRefGoogle Scholar
  8. 8.
    D. Portilla and A.R. Morrison, Bradykinin-induced changes in inositol trisphosphate mass in MDCK cells, BBRC 140:644–649 (1986).PubMedGoogle Scholar
  9. 9.
    D.A. Troyer, J.I. Kreisberg, D.W. Schwertz, M. Venkatachalam, Effects of vasopressin on phosphoinositide and prostaglandin production in cultured mesangial cells.Google Scholar
  10. 10.
    K.A. Hruska, M. Goligorsky, J. Schoble, M. Tsutsumi, S. Westbrook, D. Moskowitz, Effects of parathyroid hormone on cytosolic calcium in renal proximal tubule primary cultures, Am. J. Physiol. 251:F188–F198 (1986).PubMedGoogle Scholar
  11. 11.
    M.S. Goligorsky, D.J. Loftus, K.A. Hruska, Cytoplasmic calcium in individual proximal tubular cells in culture, Am. J. Physiol. 251:F938–F944 (1986).PubMedGoogle Scholar
  12. 12.
    S.L. Hofmann and P.W. Majerus, Purification and properties of phosphatidylinositol specific phospholipase C from sheep seminal vesicular glands, J. Biol. Chem. 257:6461–6467 (1982).PubMedGoogle Scholar
  13. 13.
    M.G. Low, R.C. Carroll, W.B. Weglicki, Multiple forms of phosphoinositide-specific phospholipase C of different relative molecular masses in animal tissue, Biochem. J. 221:813–820 (1984).Google Scholar
  14. 14.
    M.G. Low, R.C. Carroll, A.C. Cox, Characterization of multiple forms of phosphoinositide-specific phospholipase C purified from human platelets, Biochem. J. 237:139–145 (1986).Google Scholar
  15. 15.
    S. Cockcroft, The dependence on Ca2+ of the guanine-nucleo tide-activated polyphosphoinositide phosphodiesterase in neutrophil plasma membrane, Biochem. J. 240:503–507 (1986).PubMedGoogle Scholar
  16. 16.
    S. Cockcroft, J.A. Taylor, Fluoroaluminates mimic guanosine 5′[γ-thio]-triphosphate in activating the polyphosphoinositide phosphodiesterase of hepatocyte membranes, Biochem. J. 241:409–414 (1987).PubMedGoogle Scholar
  17. 17.
    D.B. Wilson, T.E. Bross, S.L. Hoffmann, P.W. Majerus, Hydrolysis of polyphosphoinositides by purified sheep seminal vesicle phospholipase C enzymes, J. Biol. Chem. 259:11718–11724 (1984).PubMedGoogle Scholar
  18. 18.
    R.M. Dawson, N. Freinkel, F.B. Jungalwala, N. Clarke, The enzymatic formation of myoinositol 1,2 cyclic phosphate from phosphatidylinositol, Biochem. J. 122:605–607 (1971).PubMedGoogle Scholar
  19. 19.
    P.W. Majerus, T.M. Connolly, H. Deckmyn, T.S. Ross, T. E. Bross, H. Ishii, V.S. Bansal, D.B. Wilson, The metabolism of phosphoinositide devoid messenger molecules, Science 234:1519–1526 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    J.A. Shayman, R.J. Auchus, A.R. Morrison, Bradykinin-induced changes in myo-inositol 1,2 (cyclic) phosphate in rabbit papillary collecting tubule cells, Biochem. Biophys. Acta. 888:171–175 (1986).PubMedCrossRefGoogle Scholar
  21. 21.
    D.B. Wilson, T.E. Bross, W.R. Sherman, R.A. Berger, P.W. Majerus, Inositol cyclic phosphates are produced by cleavage of phosphatidylphos-phoinositols (polyphosphoinositide) with purified sheep seminal vesicle phospholipase C enzymes, Proc. Natl. Acad. Sci. 82:4013–4017 (1985).PubMedCrossRefGoogle Scholar
  22. 22.
    D.B. Wilson, T. Connolly, T.E. Bross, P.W. Majerus, W.R. Sherman, A. Tyler, L.J. Rubin, J.E. Brown, Isolation and characterization of the inositol cyclic phosphate products of polyphosphoinositide cleavage by phospholipase C, J. Biol. Chem. 260:13496–13581 (1985).PubMedGoogle Scholar
  23. 23.
    R.F. Irvine, A.J. Letcher, D.J. Lander, M.S. Berridge, Specificity of inositol phosphate-stimulated Ca2+ mobilization from Swiss mouse 3T3 cells, Biochem. J. 240:301–304 (1986).Google Scholar
  24. 24.
    F.A. O’Rourke, S.P. Halenda, G.B. Zavoico, M.B. Feinstein, Inositol 1, 4, 5 trisphosphate releases Ca2+ from a Ca2+ -transporting membrane vesicle fraction derived from human platelets, J. Biol. Chem. 260:956–962 (1985).PubMedGoogle Scholar
  25. 25.
    I.R. Batty, S.R. Nahorski, R.F. Irvine, Rapid formation of inositol 1, 3, 4, 5 tetrakis phosphate following muscarinic receptor stimulation of rat cerebral cortical slices, Biochem. J. 232:211–215 (1985).PubMedGoogle Scholar
  26. 26.
    R.F. Irvine, A.J. Letcher, J.P. Heslop, M.J. Berridge, The inositol tris/tetrakisphosphate pathway — demonstration of Ins(1, 4, 5)P33-kinase activity in animal tissues, Nature (London) 320:631–634 (1986).CrossRefGoogle Scholar
  27. 27.
    C.A. Hansener, S. Mah, J.R. Williamson, Formation and metabolism of inositol 1, 3, 4, 5 tetrakisphosphate in liver, J. Biol. Chem. 261: 8100–8103 (1986).Google Scholar
  28. 28.
    R.F. Irvine, A.J. Letcher, D.J. Lander, J.P. Heslop, M.J. Berridge, Inositol(3, 4) bisphosphate and inositol(l,3) bisphosphate in GH4 cells — evidence for complex breakdown of inositol(1, 3, 4) bisphosphate, BBRC 143:353–359 (1987).PubMedGoogle Scholar
  29. 29.
    R.C. Inborn, V.S. Bansal, P.W. Majerus, Pathway for inositol 1, 3, 4 trisphosphate and 1,4 bisphosphate metabolism, Proc. Natl. Acad. Sci. 84: 2170–2174 (1987).CrossRefGoogle Scholar
  30. 30.
    C.D. Downes, M.C. Mussat, R.H. Michell, The inositol trisphosphate Phosphomonoesterase of the human erythrocyte membrane, Biochem. J. 203: 169–177 (1982).PubMedGoogle Scholar
  31. 31.
    G.J. Tertoolen, B.C. Tilly, R.F. Irvine, W.H. Moolenaar, Electrophysiological responses to bradykinin and microinjected polyphosphates in neuroblastoma cells. Possible role of inositol 1,3,A trisphosphate in altering membrane potential, FEBS Lett. 214:365–369 (1987).PubMedCrossRefGoogle Scholar
  32. 32.
    R.F. Irvine and R.M. Moor, Microinjection of inositol 1, 3, 4, 5 tetrakisphosphate activates sea urchin eggs by a mechanism dependent in external Ca2+, Biochem. J. 240:917–920 (1986).PubMedGoogle Scholar
  33. 33.
    M.D. Honsay, Egg activation unscrambles a potential role for IP4, TIBS 12:133–134 (1987).Google Scholar
  34. 34.
    Y. Takai, U. Kikkawa, Y. Kaibuchi, Y. Nishizuka, Membrane phospholipid metabolism and signal transduction for protein phosphorylation, Adv. Cyclic Nucl. Protein Phos. Res. 18:119–158 (1984).Google Scholar
  35. 35.
    A.M. Speigel, Signal transduction by guanine nucleotide binding proteins, Molecular and Cellular Endocrinology 49:1–16 (1987).CrossRefGoogle Scholar
  36. 36.
    M. Oinuma, T. Katuda, M. Ui, A new GTP-binding protein in differentiated Human Leukenic (HL-60) cells serving as the specific substrate of islet activating protein pertussis toxin, J. Biol. Chem. 262:8347–8353 (1987).PubMedGoogle Scholar
  37. 37.
    I. Magnaldo, H. Talwar, W.D. Anderson, J. Pouyssegur, Evidence for a GTP-binding protein coupling thrombin receptor to PIP2-phospho-lipase C in membranes of hamster fibroblasts, FEBS Lett. 210:6–10 (1987).PubMedCrossRefGoogle Scholar
  38. 38.
    S. Cockcroft, The dependence on Ca2+ of the guanine nucleotide-activated polyphosphoinositide phosphodiesterase in neutrophil plasma membranes, Biochem. J. 240:503–507 (1986).PubMedGoogle Scholar
  39. 39.
    G.M. Bokoch and A.G. Gilman, Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin, Cell 39:301–308 (1984).PubMedCrossRefGoogle Scholar
  40. 40.
    P.C. Grenier, T.E. Rollins, W.L. Smith, Kinin induced prostaglandin synthesis by renal papillary collecting tubule cells in culture, Am. J. Physiol. F94–F104 (1981).Google Scholar
  41. 41.
    J.A. Shayman, K. Hruska, A.R. Morrison, Bradykinin stimulates increased intracellular calcium in papillary collecting tubules of the rabbit, Biochem. Biophys. Res. Comm. 134:299–306 (1986).PubMedCrossRefGoogle Scholar
  42. 42.
    P.C. Isakson, A. Raz, S.E. Denny, A. Wyche, P. Needleman, Hormonal stimulation of arachidonate release from isolated perfused organs: relationship to prostaglandin biosynthesis, Prostaglandins 14:853–871 (1977).PubMedCrossRefGoogle Scholar
  43. 43.
    J.A. Shayman, R.J. Auchas, A.R. Morrison, Bradykinin-induced changes in myoinositol 1,2(cyclic) phosphate in rabbit papillary collecting tubule cells, Biochem. Biophys. Acta. 888:171–175 (1986).PubMedCrossRefGoogle Scholar
  44. 44.
    R.M. Zusman, J.R. Keiser, J.E. Handler, Vasopressin-stimulated prostaglandin E biosynthesis in the toad urinary bladder, J. Clin. Invest. 60:1339–1347 (1977).PubMedCrossRefGoogle Scholar
  45. 45.
    J.E. Bisordi, D. Schlondorff, R.M. Hayes, Interaction of vasopressin and prostaglandins in the toad urinary bladder, J. Clin. Invest. 66: 1200–1210 (1980).PubMedCrossRefGoogle Scholar
  46. 46.
    J.M. Forrest, C.J. Schneider, D.B. Goodman, Role of prostaglandin E2 in mediating the effects of pH on the hydrosomotic response to vasopressin in the toad urinary bladder, J. Clin. Invest. 69:499–506 (1982).PubMedCrossRefGoogle Scholar
  47. 47.
    R.M. Burch and P.V. Halushka, Vasopressin stimulates prostaglandin and thromboxane synthesis in toad bladder epithelial cells, Am. J. Physiol. 243:F593–F597 (1982);PubMedGoogle Scholar
  48. 48.
    M. Sato and M. Dunn, Interactions of vasopressin, prostaglandins, and cAMP in rat renal papillary collecting tubule cells in culture, Am. J. Physiol. 247:F423–F433 (1984).PubMedGoogle Scholar
  49. 49.
    A. Garcia-Perez and W.L. Smith, Use of monoclonal antibodies to isolate cortical collecting tubule cells: AVP induces PGE release, Am. J. Physiol. 244:C211–C220 (1983).PubMedGoogle Scholar
  50. 50.
    M. Kirschenbaum, A.G. Lower, W. Trizma, L.G. Fine, Regulation of vasopressin action by prostaglandins, J. Clin. Invest. 70:1193–1204 (1982).PubMedCrossRefGoogle Scholar
  51. 51.
    B.M. Altura, Selective microvascular constrictor actions of some neurohypophyseal peptides, Eur. J. Pharmacol. 24:43–60 (1973).CrossRefGoogle Scholar
  52. 52.
    B.M. Altura and B.T. Altura, Actions of vasopressin, oxytocin, and synthetic analogs on vascular smooth muscle, Fed. Proc. 43:80–86 (1984).PubMedGoogle Scholar
  53. 53.
    J. Grantham and J. Orloff, Effect of prostaglandin E1 on the permeability response of the isolated collecting tubule to vasopressin, adenosine 3′-5′-monophosphate, and theophylline, J. Clin. Invest. 47:1154–1161 (1968).PubMedCrossRefGoogle Scholar
  54. 54.
    S.Z. Katasic, J.T. Shepherd, P.M. Van Loutte, Vasopressin causes endothelium -dependent relaxations of the canine basilar artery, Circ. Res. 55:575–579 (1984).Google Scholar
  55. 55.
    T. Nabika, P.A. Velletri, W. Lovenberg, M. Beaven, Increase in cytosolic calcium and phosphoinositide metabolism induced by angiotensin II and [Arg]vasopressin in vascular smooth muscle cells, J. Biol. Chem. 260:4661–4670 (1985).PubMedGoogle Scholar
  56. 56.
    D. Rhodes, V. Prpic, J.H. Exton, P.F. Blackmore, Stimulation of phosphatidylinositol 4,5-bisphosphate hydrolysis in hepatocytes by vasopressin, J. Biol. Chem. 258:2770–2773 (1983).PubMedGoogle Scholar
  57. 57.
    J.R. Williamson, R.H. Cooper, K.J. Suresh, A.L. Thomas, Inositol trisphosphate and diacylglycerol as intracellular second messengers in liver, Am. J. Physiol. 248:C203–C216 (1985).PubMedGoogle Scholar
  58. 58.
    S.N. Prescott and P.W. Majerus, Characterization of 1, 2-diacylglycerol hydrolysis in human platelets, J. Biol. Chem. 258:764–769 (1983).PubMedGoogle Scholar
  59. 59.
    L.M. Hallacher and W.R. Sherman, The effects of lithium ion and other agents on the activity of myoinositol-1-phosphatase from bovine brain, J. Biol. Chem. 255:10896–10901 (1980).Google Scholar
  60. 60.
    L.R. Chase and G.D. Aurbach, Parathyroid function and renal excretion of 3′5′ adenylic acid, Proc. Natl. Acad. Sci. USA 58:518–525 (1967).PubMedCrossRefGoogle Scholar
  61. 61.
    D. Charbardes, M. Imbert, A. Clique, M. Montegut, F. Morel, PTH-sensitive adenylate cyclase activity of the rabbit nephron, Pflugers Arch. 354:229 (1975).CrossRefGoogle Scholar
  62. 62.
    Z.S. Agus, L.B. Gardner, L.H. Beck, M. Goldberg, Effects of parathyroid hormone on renal tubular reabsorption of calcium, sodium and phosphate, Am. J. Physiol. 224:1143–1148 (1973).PubMedGoogle Scholar
  63. 63.
    K. Kurokawa, T. Ohno, H. Rasmussen, Ionic control of renal gluconeogenesis II. Effects of Ca2+ and H+ upon response to parathyroid hormone and cyclic AMP, Biochim. Biophys. Acta. 313:32–41 (1973).PubMedCrossRefGoogle Scholar
  64. 64.
    Z.S. Agus, J.B. Puschett, D. Senesky, M. Goldberg, Mode of action of parathyroid hormone and cyclic adenosine 3′5′-monophosphate on renal tubular phosphate reabsorption in the dog, J. Clin. Invest. 50:617–626 (1971).PubMedCrossRefGoogle Scholar
  65. 65.
    M.R. Hammerman and K.A. Hruska, Cyclic AMP-dependent protein phosphorylation in canine renal brush-border membrane vesicles is associated with decreased phosphate transport, J. Biol. Chem. 257:992–999 (1982).PubMedGoogle Scholar
  66. 66.
    M.R. Hammerman, V.A. Hansen, J.J. Morrissey, Cyclic AMP-dependent protein phosphorylation and dephosphorylation alter phosphate transport in canine renal brush border vesicles, Biochim. Biophys. Acta. 755: 10–16 (1983).PubMedCrossRefGoogle Scholar
  67. 67.
    N. Yanagawa and O.D. Jo, Possible role of calcium mediators in parathyroid hormone action on phosphate transport in rabbit renal brush border membrane, BBRC 128:278–284 (1985).PubMedGoogle Scholar
  68. 68.
    N. Yanagawa and O.D. Jo, Possible role of calcium in parathyroid hormone actions in rabbit renal proximal tubules, Am. J. Physiol. 250: F942–F948 (1986).PubMedGoogle Scholar
  69. 69.
    T.D. McKinney and P. Myers, PTH inhibition of bicarbonate transport by proximal convoluted tubules, Am. J. Physiol. 239:F127–F134 (1980).PubMedGoogle Scholar
  70. 70.
    S. Sabatini, Parathyroid hormone inhibits water flow in isolated toad bladder, Am. J. Physiol. 250:F532–F538 (1986).PubMedGoogle Scholar
  71. 71.
    P.A. Mennes, J. Yates, S. Klahr, Effects of ionophore A23187 and external calcium concentrations on renal gluconeogenesis, Proc. Soc. Exp. Med. 157:168–174 (1978).Google Scholar
  72. 72.
    N. Yanagawa, Cytosolic free calcium in isolated perfused rabbit proximal tubules: effect of parathyroid hormone (Abstract), Kidney Int. 31:361(A) (1987).Google Scholar
  73. 73.
    G.M. Dolson, M.K. Hise, E.J. Weinman, Relationship among parathyroid hormone, cAHP, and calcium on proximal tubule sodium transport, Am. J. Physiol. 249:F409–F416 (1985).PubMedGoogle Scholar
  74. 74.
    C. Kleeman, D. Yamaguchi, S. Muallem, Regulation of parathyroid hormone-activated calcium channel by phorbol ester, Kidney Int. 31:351(A) (1987).Google Scholar
  75. 75.
    A. Besarab and J.W. Swanson, Tachyphylaxis to PTH in the isolated perfused rat kidney: resistance of anticalciuria, Am. J. Physiol. 247: F240–F245 (1984).PubMedGoogle Scholar
  76. 76.
    P. Bidot-Lopez, R.V. Farese, M.A. Sabiro, Parathyroid hormone and adenosine 3′,5′ monophosphate acutely increases phospholipids of the phosphatidate-polyphosphoinositide pathway in rabbit kidney cortex tubules in vitro by a cycloheximide-sensitive process, Endocrinology 108:2078–2081 (1981).PubMedCrossRefGoogle Scholar
  77. 77.
    V. Metzler, S. Weinreb, E. Bellorin-Font, K.A. Hruska, Parathyroid hormone stimulation of renal phosphoinositide metabolism is a cyclic nucleotide-independent effect, Biochim. Biophys. Acta. 712:258–267 (1982).CrossRefGoogle Scholar
  78. 78.
    H. Lo,. D.C. Lehotay, D. Katz, G.S. Levey, Parathyroid hormone-mediated incorporation of 32P-orthophosphate into phosphatidic acid and phosphatidylinositol in renal cortical slices, Endocrin. Res. Commun. 3(Suppl. 6):377–385 (1976).Google Scholar
  79. 79.
    K.A. Hruska, D. Moskowitz, P. Esbrit, R. Civitelli, S. Westbrook, M. Huskey, Stimulation of inositol triphosphate and diacylglycerol production in renal tubular cells by parathyroid hormone, J. Clin. Invest. 79:230–239 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Aubrey R. Morrison
    • 1
  • Didier Portilla
    • 1
  • Daniel Coyne
    • 1
  1. 1.Departments of Medicine and PharmacologyWashington University School of MedicineSt. LouisUSA

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