Skip to main content
SpringerLink
Log in

The chromogranins: Their roles in secretion from neuroendocrine cells and as markers for neuroendocrine neoplasia

  • Review
  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Chromogranins are the major components of the secretory granules of most neuroendocrine cells. Within the secretory pathway, chromogranins are involved in granulogenesis, and in sorting and processing of secretory proteincargo prior to, secretion. Once secreted, they have hormonal, autocrine, and paracrine activities. The chromogranin family includes chromogranins A (CgA) and B (CgB)and secretogranin II (Sgll, once called chromogranin C). The related “granins” NESP55, 7B2, secretogranin III/1B 1075 (SgIII), and secretogranin IV/HISL-19 antigen (SgIV), are also sometimes included when considering the chromogranins. While it is useful to consider the granin proteins as a family with many common features, it is also necessary to examine the distinct features and properties of individual members of the granin family to understand fully their functions, employ them efficiently as tissue, serum, and urinary markers for neuroendocrine neoplasia, and develop an evolutionary-biologic perspective on their contribution to mammalian physiology. Recent advances in chromogranin research include establishing the role of CgA in granulogenesis and the role of CgB in nuclear transcription; new biologic activities for CgA-, CgB-, and SgII-derived peptides; and new marker functions for granins and their proteolytically processed products in endocrine neoplasias

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Banks P, Helle K. The release of protein from the stimulated adrenal medulla. Biochem J 97:40C-41C, 1965.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Kirshner N, Sage HJ, Smith WJ, et al. Release of catecholamines and specific protein from adrenal glands. Science 154:529–531, 1966.

    Article  CAS  PubMed  Google Scholar 

  3. Banks P, Helle KB, Mayor D. Evidence for the presence of a chromogranin-like protein in bovine splenic nerve granules. Mol Pharmacol 5:210–212, 1968.

    Google Scholar 

  4. Blaschko H, Comline RS, Schneider FH, et al. Secretion of a chromaffin granule protein, chromogranin, from the adrenal gland after splanchnic stimulation. Nature 215:58–59, 1967.

    Article  CAS  PubMed  Google Scholar 

  5. Cohn DV, Morrissey JJ, Hamilton JW, et al. Isolation and partial characterization of secretory protein I from bovine parathyroid glands. Biochemistry 20:4135–4140, 1981.

    Article  CAS  PubMed  Google Scholar 

  6. Cohn DV, Zangerle R, Fischer-Colbrie R, et al. Similarity of secretory protein I from parathyroid gland to chromogranin A from adrenal medulla. Proc. Natl Acad Sci USA 79:6056–6059, 1982.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Iacangelo A, Affolter HU, Eiden LE, et al. Bovine chromogranin A sequence and distribution of its messenger RNA in endocrine tissues. Nature 323:82–86, 1986.

    Article  CAS  PubMed  Google Scholar 

  8. O'Connor DT. Chromogranin: widespread immunoreactivity in polypeptide hormone producing tissues and in serum. Regul Pep 6:263–280, 1983.

    Article  Google Scholar 

  9. Fischer-Colbrie R, Lassmann H, Hagn C, et al. Immunological studies on the distribution of chromogranin A and B in endocrine and nervous tissues. Neuroscience 16:547–555, 1985.

    Article  CAS  PubMed  Google Scholar 

  10. Fischer-Colbrie R, Hagn C, Kilpatrick L, et al. Chromogranin C: a third component of the acidic proteins in chromaffin granules. J Neurochem 47:318–321, 1986.

    Article  CAS  PubMed  Google Scholar 

  11. Rosa P, Hille A, Lee RWH, et al. Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway. J Cell Biol 101:1999–2011, 1985.

    Article  CAS  PubMed  Google Scholar 

  12. Eiden LE, Huttner WB, Mallet J, et al. A nomenclature proposal for the chromogranin/secretogranin proteins. Neuroscience 21:1019–1021, 1987.

    Article  CAS  PubMed  Google Scholar 

  13. Helle KB, Aunis D, eds. Chromogranins: functional and clinical aspects. New York: Kluwer Academic/Plenum, 2000; 404.

    Google Scholar 

  14. Fischer-Colbrie R, Eder S, Lovisetti-Scamihorn P, et al. Neuroendocrine secretory protein 55: a novel marker for the constitutive secretory pathway. Ann NY Acad Sci 971:317–322, 2002.

    Article  CAS  PubMed  Google Scholar 

  15. Hashimoto S, Fumagalli G, Zanini A, et al. Sorting of three secretory proteins to distinct secretory granules in acidophilic cells of cow anterior pituitary. J Cell Biol 105:1579–1586, 1987.

    Article  CAS  PubMed  Google Scholar 

  16. Natori S, Huttner WB. Chromogranin B (secretogranin I) promotes sorting to the regulated secretory pathway of processing intermediates derived from a peptide hormone precursor. Proc Natl Acad Sci USA 93:4431–4436, 1996.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Jain RK, Joyce PBM, Gorr S-U. Aggregation chaperones enhance aggregation and storage of secretory proteins in endocrine cells. J Biol Chem 275:27,032–27,036, 2000.

    Article  CAS  Google Scholar 

  18. Gorr S-U, Jain RK, Kuehn U, et al. Comparative sorting of neuroendocrine secretory proteins: a search for common ground in a mosaic of sorting models and mechanisms. Mol Cell Endocrinol 172:1–6, 2001

    Article  CAS  PubMed  Google Scholar 

  19. Kim T, Tao-Cheng J-H, Eiden LE, et al. Chromogranin A, an “on/off” switch controlling dense-core secretory granule biogenesis. Cell 106:1–13, 2001.

    Article  Google Scholar 

  20. Reiffen FU, Gratzl M. Chromogranins, widespread in endocrine and nervous tissue, bind Ca2+ FEBS Lett 195:327–330, 1986.

    Article  CAS  PubMed  Google Scholar 

  21. Yoo SH, Albanesi JP. High capacity, low affinity Ca2+ binding of chromogranin A. J Biol Chem 266:7740–7745, 1991.

    CAS  PubMed  Google Scholar 

  22. Yoo S-H. pH- and Ca2+-induced conformational change and aggregation of chromogranin B: comparison with chromogranin A and implication in secretory vesicle biogenesis. J Biol Chem 270:12,578–12,583, 1995.

    Article  CAS  Google Scholar 

  23. Gerdes H-H, Rosa P, Phillips E, et al. The primary structure of human secretogranin II, a widespread tyrosine-sulfared secretory granule protein that exhibits low pH- and calcium-induced aggregation. J Biol Chem 264:12,009–12,015, 1989.

    CAS  Google Scholar 

  24. Hwang JR, Lindberg I. Inactivation of the 7B2 inhibitory CT peptide depends on a cal study of hormone production and chromogranin localization. Am J Pathol 116:464–472, 1984.

    Google Scholar 

  25. Cohn DV, Elting JJ, Frick M, et al. Selective localization of the parathyroid secretory protein-I/adrenal medulla chromogranin A family in a wide variety of endocrine cells of the rat. Endocrinology 114:1963–1974, 1984.

    Article  CAS  PubMed  Google Scholar 

  26. Sankoorikal BJ, Zhu YL, Hodsdon ME, et al. Aggregation of human wild-type and H27A-prolactin in cells and in solution: roles of Zn2+, Cu2+, and pH. Endocrinology 143:1302–1309 2002.

    Article  CAS  PubMed  Google Scholar 

  27. Watanabe T, Uchiyama Y, Grube D. Topology of chromogranin A and secretogranin II in the rat anterior pituitary: potential marker proteins for distinct secretory pathways in gonadotrophs. Histochemistry 96:285–293, 1991.

    Article  CAS  PubMed  Google Scholar 

  28. Sarac MS, Zieske AW, Lindberg I. The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities. Endocrinology 143:2324–2332, 2002.

    CAS  PubMed  Google Scholar 

  29. Laurent V, Kimble A, Peng B, et al. Mortality in 7B2 null mice can be rescued by adrenalectomy: involvement of dopamine in ACTH hypersecretion. Proc Natl Acad Sci USA 99:3087–3092, 2002.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Chanat E, Huttner WB. Milieu-induced, selective aggregation of regulated secretory proteins in the trans-Golgi network. J Cell Biol 115:1505–1519, 1991.

    Article  CAS  PubMed  Google Scholar 

  31. Rosa P, Zanini A. Characterization of adenohypophysial polypeptides by two-dimensional gel electrophoresis. II. Sulfated and glycosylated polypeptides. Mol Cell Endocrinol 24:181–193, 1981.

    Article  CAS  PubMed  Google Scholar 

  32. Fischer-Colbrie R, Laslop A, Kirchmair R. Secretogranin II: molecular properties, regulation of biosynthesis and processing to the neuropeptide secretoneurin. Prog Neurobiol 46:49–70, 1995.

    Article  CAS  PubMed  Google Scholar 

  33. Settleman J, Nolan J, Angeletti RH. Chromogranin, an integral membrane protein. J Biol Chem 260:1641–1644, 1985.

    CAS  PubMed  Google Scholar 

  34. Pimplikar SW, Huttner WB. Chromogranin B (secretogranin I), a secretory protein of the regulated pathway, is also p9resent in a tightly membrane-associated form in PC12 cells. J Biol Chem 267:4110–4118, 1992.

    CAS  PubMed  Google Scholar 

  35. Yoo SH, So SH, Kweon HS, et al. Coupling of the inositol 1,4,5-trisphosphate receptor and chromogranins A and B in secretory granules. J Biol Chem 275:12,553–12,559, 2000

    Article  CAS  Google Scholar 

  36. Yoo SH. Coupling of the IP3 receptor/Ca2+ channel with Ca2+storage proteins chromogranins A and B in secretory granules. Trends Neurosci 23:424–428, 2000.

    Article  CAS  PubMed  Google Scholar 

  37. Iguchi H, Chan JSD, Seidah NG, et al. Tissue distribution and molecular forms of a novel pituitary protein in the rat. Neuroendocrinology 39:453–458, 1984.

    Article  CAS  PubMed  Google Scholar 

  38. Ottiger H-P, Battenberg EF, Tsou A-P, et al. IB1075: a brain-and pituitary-specific mRNA that encodes a novel chromogranin/secretogranin-like component of intracellular vesicles. J Neurosci 10:3135–3147, 1990.

    CAS  PubMed  Google Scholar 

  39. Sichia R, Lovisetti-Scamihorn P, Hogue-Angeletti R, et al. Molecular cloning and characterization of NESP55, a novel chromogranin-like precursor of a peptide with 5-HTIB receptor antagonist activity. J Biol Chem 272:11,657–11,662, 1997.

    Article  Google Scholar 

  40. Fasciotto BH, Gorr S-U, Cohn DV. Autocrine inhibition of parathyroid cell secretion requires proteolytic processing of chromogranin A. Bone Min 17:323–333, 1992.

    Article  CAS  Google Scholar 

  41. Egger C, Kirchmair R, Hogue-Angeletti R, et al. Different degrees of processing of secretogranin II in large dense core vesicles of bovine adrenal medulla and sympathetic axons correlate with their content of soluble PC1 and PC2. Neurosci Lett 159:199–201, 1993.

    Article  CAS  PubMed  Google Scholar 

  42. Arden SD, Rutherford NG, Guest PC, et al. The post-translational processing of chromogranin A in the pancreatic islet: involvement of the eukaryote subtilisin PC2. Biochem J 298:521–528, 1994.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Laslop A, Weiss C, Savaria D, et al. Proteolytic processing of chromogranin B and secretogran in II by prohormone convertases. J Neurochem 70:374–383, 1998.

    Article  CAS  PubMed  Google Scholar 

  44. Laslop A, Becker A, Lindberg I, et al. Proteolytic processing of chromogranins is modified in brains of transgenic mice. Ann NY Acad Sci 271:49–52, 2002.

    Article  Google Scholar 

  45. Stridsberg M, Angeletti RH, Helle KB. Characterisation of N-terminal chromogranin A and chromogranin B in mammals by region-specific radioimmunoassays and chromatographic separation methods. J Endocrinol 165:703–714, 2000.

    Article  CAS  PubMed  Google Scholar 

  46. Borch K, Stridsberg M, Burman P, et al. Basal chromogranin A and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-A gastritis. Scand J Gastroenterol 32:198–202, 1997.

    Article  CAS  PubMed  Google Scholar 

  47. Kirchmair R, Egger C, Gee P, et al. Differential subcellular distribution of PC1, PC2 and furin in bovine adrenal medulla and secretion of PC1 and PC2 from this tissue. Neurosci Lett 143:143–145, 1992.

    Article  CAS  PubMed  Google Scholar 

  48. Winkler H, Fischer-Colbrie R. The chromogranins A and B: the first 25 years and future perspectives. Neuroscience 49:497–528, 1992.

    Article  CAS  PubMed  Google Scholar 

  49. Metz-Boutigue M-H, Garcia-Sablone P, Hogue-Angeletti R, et al. Intracellular and extracellular processing of chromogranin A: determination of cleavage sites. Eur J Biochem 217:247–257, 1993.

    Article  CAS  PubMed  Google Scholar 

  50. Jiang Q, Yasothornsrikul S, Taupenot L, et al. The local chromaffin cell plasminogen/plasmin system and the regulation of catecholamine secretion. Ann NY Acad Sci 971:445–449, 2002.

    Article  CAS  PubMed  Google Scholar 

  51. Fasciotto BH, Denny JC, Greeley GH Jr, et al. Processing of chromogranin A in the parathyroid: generation of parastatin-related peptides. Peptides 21:1389–1401, 2000.

    Article  CAS  PubMed  Google Scholar 

  52. Seidah NG, Hendy GN, Hamelin J, et al. Chromogranin A can act as a reversible processing enzyme inhibitor: evidence from the inhibition of the IRCM-serine protease 1 cleavage of pro-enkephalin and ACTH at pairs of basic amino acids. FEBS Lett 211:144–150, 1987.

    Article  CAS  PubMed  Google Scholar 

  53. Helle KB, Angeletti RH. Chromogranin A: a multipurpose prohormone? Acta Physiol Scand 152:1–10, 1994.

    Article  CAS  PubMed  Google Scholar 

  54. Iacangelo AL, Eiden LE. Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway. Regul Pep 58:65–88, 1995.

    Article  CAS  Google Scholar 

  55. Helle KB, Metz-Boutigie M-H, Aunis D. Chromogranin A as a calcium-binding precusor for a multitude of regulatory peptides for the immune, endocrine and metabolic systems. Curr Med Chem-Immun Endocr Metab Agents 1:119–140, 2001.

    Article  CAS  Google Scholar 

  56. Aardal S, Helle KB. The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its independence of extracellular calcium in isolated segments of human blood vessels. Regul Pep 41:9–18, 1992.

    Article  CAS  Google Scholar 

  57. Aardal S, Helle KB, Elsayed S, et al. Vasostatins, comprising the N-terminal domain of chromogranin A, suppress tension in isolated human blood vessel segments. J Neuroendocrinol 5:405–412, 1993.

    Article  CAS  PubMed  Google Scholar 

  58. Angeletti RH, Aardal S, Serck-Hanssen G, et al. Vasoinhibitory activity of synthetic peptides from the amino terminus of chromogranin A. Acta Physiol Scand 152:11–19, 1994.

    Article  CAS  PubMed  Google Scholar 

  59. Sanchez-Margalet V, Gonzalez-Yanes C, Santos-Alvarez J, et al. Pancreastatin: biological effects and mechanisms of action. Adv Exp Med Biol 482:247–262, 2000.

    Article  CAS  PubMed  Google Scholar 

  60. Sanchez-Margalet V, Gonzalez-Yanes C. Pancreastatin inhibits insulin action in rat adipocytes. Am J Physiol 275:E1055-E1060, 1998.

    CAS  PubMed  Google Scholar 

  61. Gonzalez-Yanes C, Sanchez-Margalet V. Pancreastatin modulates insulin signaling in rat adipocytes: mechanisms of cross-talk. Diabetes 49:1288–1294, 2000.

    Article  CAS  PubMed  Google Scholar 

  62. Tatemoto K, Efendic S, Mutt V, et al. Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 324:476–478, 1986.

    Article  CAS  PubMed  Google Scholar 

  63. Taupenot L, Ciesielski-Treska J, Ulrich G, et al. Chromogranin A triggers a phenotypic transformation and the generation of nitric oxide in brain microglial cells. Neuroscience 72:377–389, 1996.

    Article  CAS  PubMed  Google Scholar 

  64. Sanchez-Margalet V, Lucas M, Goberna R. Pancreastatin action in the liver: dual coupling to different G proteins. Cell Signal 8:9–12, 1996.

    Article  CAS  PubMed  Google Scholar 

  65. Gonzalez-Yanes C, Santos-Alvarez J, Sanchez-Margalet V. Characterization of pancreastatin receptors and signaling in adipocyte membranes. Biochim Biophys Acta 1451: 153–162, 1999.

    Article  CAS  PubMed  Google Scholar 

  66. Schneitler C, Kahler C, Wiedermann CJ, et al. Specific binding of a 1251-secretoneurin analogue to a human monocytic cell line. J Neuroimmunol 86:87–91, 1998.

    Article  CAS  PubMed  Google Scholar 

  67. Lembo PM, Grazzini E, Groblewski T, et al. Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nat Neurosci 5:201–209, 2002.

    Article  CAS  PubMed  Google Scholar 

  68. Rieker S, Fischer-Colbrie R, Eiden L, et al. Phylogenetic distribution of peptides related to chromogranins A and B. J. Neurochem 50:1066–1073, 1988.

    Article  CAS  PubMed  Google Scholar 

  69. Peterson JB, Nelson DL, Ling E, et al. Chromogranin A-like proteins in the secretory granules of a protozoan, Paramecium tetraurelia. J Biol Chem 262:17,264–17,267, 1987.

    CAS  Google Scholar 

  70. Brownlee DJA, Fairweather I, Johnston CG, et al. Immunocytochemical demonstration of neuropeptides in the central nervous system of the roundworm, Ascaris suum (Nematoda: Ascaroidea). Parasitology 106:305–316, 1993.

    Article  CAS  PubMed  Google Scholar 

  71. Smart D, Johnston CF, Curry WJ, et al. Immunoreactivity to two specific regions of chromogranin A in the nervous system of Ascaris suum: an immunocytochemical study. Parasitol Res 78:329–335, 1992.

    Article  CAS  PubMed  Google Scholar 

  72. Lindberg I, Tu B, Muller L, et al. Cloning and functional analysis of C. elegans 7B2. DNA Cell Biol 17:727–734, 1998.

    Article  CAS  PubMed  Google Scholar 

  73. Sato F, Kanno T, Nagasawa S, et al. Immunohistochemical localization of chromogranin A in the acinar cells of equine salivary glands contrasts with rodent glands. Cells Tissues Organs 172:29–36, 2002.

    Article  CAS  PubMed  Google Scholar 

  74. Elde R, Haber S, Ho R, et al. Interspecies conservation and variation in peptidergic neurons. Peptides 1:21–26, 1980.

    Article  CAS  Google Scholar 

  75. Simon J-P, Aunis D. Biochemistry of the chromogranin A protein family. Biochem J 262:1–13, 1989.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Stridsberg M, Husebye ES. Chromogranin A and chromogranin B are sensitive circulating markers for phaeochromocytoma. Eur J Endocrinol 136:67–73, 1997.

    Article  CAS  PubMed  Google Scholar 

  77. O'Connor DT, Burton D, Deftos LJ. Immunoreactive human chromogranin A in diverse polypeptide hormone producing human tumors and normal endocrine tissues. J Clin Endocrinol Metab 57:1084–1086, 1983.

    Article  PubMed  Google Scholar 

  78. Lloyd RV, Mervak T, Schmide K, et al. Immunohistochemical detection of chromogranin and neuron-specific enolase in pancreatic endocrine neoplasms. Am J Surg Pathol 8:607–614, 1984.

    Article  CAS  PubMed  Google Scholar 

  79. O'Connor DT, Burton DW, Parmer RJ, et al., in Cohn DV et al., eds., Endocrine control of bone and calcium metabolism, Amsterdam: Elsevier, 1984; 187–190.

    Google Scholar 

  80. Lloyd RV, Blaivas M, Wilson BS. Distribution of chromogranin and S100 protein in normal and abnormal adrenal medullamy tissues. Arch Pathol Lab Med 109:633–638, 1985.

    CAS  PubMed  Google Scholar 

  81. Said JW, Vimadalal S, Nash G, et al. Immunoreactive neuron-specific enolase, bombesin, and chromogranin as markers for neuroendocrine lung tumors. Hum Pathol 16:236–240, 1985.

    Article  CAS  PubMed  Google Scholar 

  82. Walts AE, Said JW, Shintaku P, et al. Chromogranin as a marker of neuroendocrine cells in cytologic material—an immunocytochemical study. Am J Clin Pathol 84:273–277, 1985.

    CAS  PubMed  Google Scholar 

  83. O'Connor DT, Deftos LJ. Secretion of chromogranin A by peptide-producing endocrine neoplasms. N Engl J Med 314:1145–1151, 1986.

    Article  PubMed  Google Scholar 

  84. Lloyd RV. Immunohistochemical localization of chromogranin in normal and neoplastic endocrine tissues. Pathol Ann 22:69–90, 1987.

    Google Scholar 

  85. Schmid KW, Fischer-Colbrie R, Hagn C, et al. Chromogranin A and B and secretogranin II in medullary carcinomas of the thyroid. Am J Surg Pathol 11:551–556, 1987.

    Article  CAS  PubMed  Google Scholar 

  86. Schober M, Fischer-Colbrie R, Schmid KW, et al. Comparison of chromogranins A, B, and secretogranin II in human adrenal medulla and pheochromocytoma. Lab Invest 57:385–391, 1987.

    CAS  PubMed  Google Scholar 

  87. Weiler R, Feichtinger H, Schmid KW, et al. Chromogranin A and B and secretogranin II in bronchial and intestinal carcinoids. Virchows Arch A Pathol Anat Histopathol 412:103–109, 1987.

    Article  CAS  PubMed  Google Scholar 

  88. Tischler AS, Dayal Y, Balogh K, et al. The distribution of immunoreactive chromogranins, S-100 protein, and vasoactive intestinal peptide in compound tumors of the adrenal medulla. Hum Pathol 18:909–917, 1987.

    Article  CAS  PubMed  Google Scholar 

  89. Weiler R, Fischer-Colbrie R, Schmid KW, et al. Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors. Am J Surg Pathol 12:877–884, 1988.

    Article  CAS  PubMed  Google Scholar 

  90. Schmid KW, Schröder S, Dockhorn-Dworniczak B, et al. Immunohistochemical demonstration of chromogranin A, chromogranin B, and secretogranin I in extra-adrenal paragangliomas. Modern Pathol 7:347–353, 1994.

    CAS  Google Scholar 

  91. Ischia R, Culig Z, Eder U, et al. Presence of chromogranins and regulation of their synthesis and processing in a neuroendocrine prostate tumor cell line. Prostate Suppl 8:80–87, 1998.

    Article  CAS  PubMed  Google Scholar 

  92. Hsiao RJ, Seeger RC, Yu AL, O'Connor DT, Chromogranin A in children with neuroblastoma serum concentration parallels disease stage and predicts survival. J Clin Invest 85:1555–1559, 1990.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  93. Eriksson B, Arnberg H, Oberg K, et al. Chromogranins—new sensitive markers for neuroendocrine tumors. Acta Oncol 28: 325–329, 1989.

    Article  CAS  PubMed  Google Scholar 

  94. Yasuda D, Iguchi H, Funakoshi A, et al. Comparison of plasma pancreastatin and GAWK concentrations, presumed procesing products of chromogranin A and B, in plasma of patients with pancreatic islet cell tumors. Horm Metab Res 25:593–595, 1993.

    Article  CAS  PubMed  Google Scholar 

  95. Iguchi H, Hara N, Hayashi I, etal. Elevation of a novel pituitary protein (7B2) in the palsma in small cell carcinoma of the lung. Eur J Cancer Clin Oncol 25:1225–1232, 1989.

    Article  CAS  PubMed  Google Scholar 

  96. Iguchi H, Niida Y, Natori S, etal. Remarkbble changes in the plasma levels of pituir∢ry protein “7B2” during childhood. Peidatr Res 24:194–196, 1988.

    Article  CAS  Google Scholar 

  97. O'Connor DT, Bernstein KN. Radioimmunoassay of chromogranin A in plasma as ameasure of exocytotic sympathoadrenal activity in normal subjects and patients with pheochromocytoma. N Engl J Med 311:764–770, 1984.

    Article  PubMed  Google Scholar 

  98. Takiyyuddin MA, Brown MR, Dinh TQ, et al. Sympathol-adrenal secretion in humans; factors governing catecholamine and storage vesicle peptide co-release. J Auton Pharmacol 14:187–200, 1994.

    Article  CAS  PubMed  Google Scholar 

  99. Kanno T, Asada N, Yanase H, et al. Salivary secretion of highly concentrated chromogranin a in respone to noradrenaline and acetylcholine in isolated and perfused rat submandibular glands. Exp Physiol 84: 1073–1083, 1999.

    Article  CAS  PubMed  Google Scholar 

  100. Yanaihara N, Kanno T, Asada N, et al. VIP-and PACAP-induced salivary chromogranin A secretion in the isolated perfused submandibular gland of rats. Ann NY Acad Sci 921:218–225, 2000.

    Article  CAS  PubMed  Google Scholar 

  101. Kanno T, Asada N, Yanase H, et al. Salivary secretion of chromogranin A: control by autonomic nervous system. Adv Exp Med Biol 482:143–51, 2000.

    Article  CAS  PubMed  Google Scholar 

  102. Steiner H-J, Weiler R, Ludescher C, et al. Chromogranins A and B are col-localized with atrial natriuretic peptides in secretory granules of rat heart. J Histochem Cytochem 38:845–850, 1990.

    Article  CAS  PubMed  Google Scholar 

  103. Hakanson R, Ding XQ, Norlen P, et al. Circulating pancreastatin is a marker for the enterochromaffin-like cells of the rat stomach. Gastroenterology 108:1445–1452, 1995.

    Article  CAS  PubMed  Google Scholar 

  104. Tateishi K, Funakoshi A, Wakasugi H, et al. Plasma pancreastatin-like immunoreactivity in various diseases. J Clin Endocrinol Metab 69:1305–1308, 1989.

    Article  CAS  PubMed  Google Scholar 

  105. Nielsen E, Welinder BS, Madsen OD. Chromogranin-B, a putative precursor of eight novel rat glucagonoma peptides through procesing at mono-, di-, or tribasic residues. Endocrinology 129:3147–3156, 1991.

    Article  CAS  PubMed  Google Scholar 

  106. Edgren M., Stridsberg M, Kalknar KM, et al. Neuroendocrine markers: chromogranin, pancreastatin and serotonin in the management of patients with advanced renal cell carcinoma. Anticancer Res 16:4871–4874, 1996.

    Google Scholar 

  107. Öberg K. Biology, diagnosis, and treament of neuroendocrine tumors of the gastrointestinal tract. Curr Opin Oncol 6:441–451, 1994.

    Article  PubMed  Google Scholar 

  108. Falkensammer G, Fischer-Colbrie R, Richter K, et al. Cell-free and cellular synthesi of chromogranin A and B of bovine adrenal medulla. Neuroscience 14:735–746, 1985.

    Article  CAS  PubMed  Google Scholar 

  109. Conn PM, Janovick JA, Braden TD, et al. SIIp: a unique secretogranin/chromogranin of the pituitary released in response to gonadotropin-releasing hormone. Endocrinology 130:3033–3040, 1992.

    CAS  PubMed  Google Scholar 

  110. Hosaka M, Watanabe T, Sakai Y, et al. Identification of a chromogranin A domain that mediates binding to secretogranin II and targeting to secretory granules in pituitary cells and pancreatic beta-cells. Mol Biol Cell 13:3388–3399, 2002.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  111. Neuhold N, Ullrich R. Secretogranin IV immunoreactivity in medullary thyroid carcinoma: an immunohistochemical study of 62 cases. Virchows Arch A Pathol Anat Histopathol 423:85–89, 1993.

    Article  CAS  PubMed  Google Scholar 

  112. Trani E, Giorgi A, Canu N, et al. Isolation and characterization of VGF peptides in rat brain: role of PC1/3 and PC2 in the maturation of VGF precursor. J Neurochem 81:565–574, 2002

    Article  CAS  PubMed  Google Scholar 

  113. Russell J, Gee P, Liu SM, et al. Inhibition of parathyroid hormone secretion by aminoterminal chromogranin peptides. Endocrinology 135:337–342, 1994.

    CAS  PubMed  Google Scholar 

  114. Lazure C, Paquet L, Litthauer D, et al. The ostrich pituitary contains a major peptide homologous to mammalian chromogranin A(1–76). Peptides 11:79–87, 1990.

    Article  CAS  PubMed  Google Scholar 

  115. Hutton JC, Davidson HW, Grimaldi KA, et al. Bisynthesis of β-granin in pancreatic β cells. Biochem J 244:449–456, 1987.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  116. Hutton JC, Davidson HW, Peshvaria M. The mechanism of chromogranin A processing. Nature 325:766, 1987.

    Article  CAS  PubMed  Google Scholar 

  117. Drees BM, Rouse J, Johnson J, et al. Bovine parathyroid glands secrete a 26-kDa N-terminal fragment of chromogranin-A which inhibits parathyroid cell secretion. Endocrinology 129:3381–3387, 1991.

    Article  CAS  PubMed  Google Scholar 

  118. Drees BM, Hamilton JW. Processing of chromogranin A by bovine parathyroid secretory granules: production and secretion of N-terminal fragments. Endocrinology 134:2057–2063, 1994.

    CAS  PubMed  Google Scholar 

  119. Sekiya K, Ghatei MA, Minamino N, et al. Isolation of human pancreastatin fragment containing the active sequence from a glucogonoma. FEBS Lett 228:153–156, 1988.

    Article  CAS  PubMed  Google Scholar 

  120. Schmidt WE, Siegel EG, Kratzin H, et al. Isolation and primary structure of tumorderived peptides related to human pancreastatin and chromogranin A. Proc Natl Acad Sci USA 85:8231–8235, 1988.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  121. Nakano I, Funkaoshi A, Miyasaka K, et al. Isolation and characterization of bovine pancreastatin. Regul Pep 25:207–213, 1989.

    Article  CAS  Google Scholar 

  122. Efendic S, Tatemoto K, Mutt V, et al. Pancreastatin and islet hormone release. Proc Natl Acad Sci USA 84:7257–7260, 1987.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  123. Ahren B, Lindskog S, Tatemoto K, et al. Pancreastatin inhibits insulin secretion and stimulates glucagon secretion in mice. Dibetes 37:281–285, 1988.

    Article  CAS  Google Scholar 

  124. Ishizuka J, Asada I, Poston GJ, et al. Effect of pancreastatin on pancreatic endocrine and exocrine secretion. Pancres 4:277–281, 1989.

    Article  CAS  Google Scholar 

  125. Lewis JJ, Zdon MJ, Adrian TE, et al. Pancreastatin: a novel peptide inhibitor of parietal cell secretion. Surgery 104:1031–1036, 1988.

    CAS  PubMed  Google Scholar 

  126. Lewis JJ, Goldenring JR, Asher VA, et al. Pancreastatin: a novel peptide inhibitor of pariental cell signal tranduction. Biochem Biophys Res Commun 163:667–673, 1989.

    Article  CAS  PubMed  Google Scholar 

  127. Drees BM, Hamilton JW. Pancreastatin and bovine parathyroid cell secretion. Bone Miner 17:335–346, 1992.

    Article  CAS  PubMed  Google Scholar 

  128. Fasciotto BH, Gorr S-U, DeFranco DJ, et al. Pancreastatin, a presumed product of chromogranin-A (secretory protrein-I procesing, inhibitis secretion from procine parathyroid cells in culture. Endocrinology 125:1617–1622, 1989.

    Article  CAS  PubMed  Google Scholar 

  129. Zhang J-X, Fasciotto BH, Darling DS, et al. Pancreastatin, a chromograin A-derived peptide, inhibits transcription of the parathyroid hormone and chromogranin A genes and decreases the stability of the respective mesenger ribonucleic acids in parathyroid cells in culture. Endocrinology 134:1310–1316, 1994.

    CAS  PubMed  Google Scholar 

  130. Funakoshi A, Miyasaka K, Kitani K, et al. Comparative effects of mammalian pancreastatins on the pancreatic exocrine secretion. Jpn J Physiol 39:901–905, 1989.

    Article  CAS  PubMed  Google Scholar 

  131. Sanchez-Margalet V, Goberna R Pancreastatin decreases plasma epinephrine levels in surgical stress in the rat. Peptides 14:797–799, 1993.

    Article  CAS  PubMed  Google Scholar 

  132. Curry WJ, Shaw C, Johnston CF, et al. Isolation and primary structure of a novel chromogranin A-derived peptide, WE-14, from a human midgut carcinoid tumour. FEBS Lett 301:319–321, 1992.

    Article  CAS  PubMed  Google Scholar 

  133. Forsythe P, Curry WJ, Johnston CF, et al. The modulatory effects of WE-14 on histamine release from rat peritoneal mast cells. Inflamm Res 46(Suppl 1):S13, S14, 1997.

    Article  Google Scholar 

  134. Tsigelny I, Mahata SK, Taupenot L, et al. Mechanism of action of chromogranin A on catecholamine release: molecular modeling of the catestatin region reveals a beta-strand/loop/beeta-strand structure secured by hydrophobic interactions and predictive of activity. Regul Rept 77:43–53, 1998.

    Article  CAS  Google Scholar 

  135. Taupenot L, Mahata SK, Mahata M, et al. Interaction of the catecholamine releaseinhibitory peptide catestatin (human chromogranin A(352-372)) with the chromaffin cell surface and Torpedo electroplax: implications for nicotinic cholinergic antagonism. Regul Pept 95:9–17, 2000.

    Article  CAS  PubMed  Google Scholar 

  136. Kennedy BP, Mahata SK, O'Connor DT, et al. Mechanism of cardiovascular actions of the chromogranin A fragment catestatin in vivo. Peptides 19:1241–1248, 1998.

    Article  CAS  PubMed  Google Scholar 

  137. Mahata SK, Mahata M, Wakade AR, et al. Primary structure and function of the carecholamine release inhibitory peptide catestatin (chromogranin A344–364): identification of amino acid residues crucial for activity. Mol Endocrinol 14:1525–1535, 2000.

    CAS  PubMed  Google Scholar 

  138. Strub JM, Guomon Y, Lugardon K, et al. Antibacterial activity of glycosylated and phosphorylated chromogranin A-derived peptide 173–194 from bovine adrenal medullary chromaffin granules. J Biol Chem 271:28,533–28,540, 1996.

    Article  CAS  Google Scholar 

  139. Funakoshi A, Jimi A, Yasunami Y, et al. Bioactivity of human pancreastatin and its localization in pancreas. Biochem Biophys Res Commun 159:913–918, 1989.

    Article  CAS  PubMed  Google Scholar 

  140. Fasciotto BH, Trauss CA, Greeley GH, Cohn DV. Parastatin (porcine chromogranin A347.419), a novel chromogranin Aderived peptide, inhibits parathyroid cell secretion. Endocrinology 133:461–466, 1993.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section on Molecular Virology (SAF) Laboratory of Cellular and Molecular Regulation, National Institutes of Health, 36 Convent Drive, MSC 4090, 20892-4090, Bethesda, MD

    Steven A. Feldman PhD & Lee E. Eiden PhD

  2. Section on Molecular Neuroscience (LEE), Laboratory of Cellular and Molecular Regulation, National Institutes of Health, 36 Convent Drive, MSC 4090, 20892-4090, Bethesda, MD

    Steven A. Feldman PhD & Lee E. Eiden PhD

Authors
  1. Steven A. Feldman PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lee E. Eiden PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feldman, S.A., Eiden, L.E. The chromogranins: Their roles in secretion from neuroendocrine cells and as markers for neuroendocrine neoplasia. Endocr Pathol 14, 3–23 (2003). https://doi.org/10.1385/EP:14:1:3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1385/EP:14:1:3

Key words

Search

Navigation