Skip to main content
Log in

Chromogranin A (CGA) in the gastro-entero-pancreatic (GEP) endocrine system

I. CGA in the mammalian endocrine pancreas

  • Published:
Histochemistry Aims and scope Submit manuscript

Summary

Chromogranin A (CGA), a protein at first detected in the adrenal medulla, has recently been found also in other organs, e.g. the endocrine pancreas. However, immunohistochemical findings concerning the cellular source of pancreatic CGA were controversial. Therefore, the endocrine pancreas of 10 mammalian species (man, tupaia, mole, cat, dog, pig, guinea pig, rabbit, rat) was investigated immunohistochemically for CGA-like immunoreactivities on serial semithin plastic sections using a high-titer polyclonal antiserum against bovine CGA. The results show that basically all pancreatic endocrine cell types are CGA-immunoreactive; however, every species has its own pattern of CGA-immunoreactive cell types. Other findings of the present studies indicate that the physiological function of CGA in pancreatic endocrine cells is related to the storage mechanisms of peptide hormones. Finally, a methodological approach is given to obtain not only qualitative but also semiquantitative data during immunohistochemical investigations.

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

Access this article

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

  • Beglinger R, Becker M, Eggenberger E, Lombard C (1975) Das Göttinger Miniaturschwein als Versuchstier. Res Exp Med 165:251–263

    Google Scholar 

  • Björklund A, Falck B, Owman Ch (1972) Eluorescence microscopic and microspectrofluorometric techniques for the cellular localization and characterization of biogenic amines. In: Rall JE, Kopin IJ (eds) Methods in investigative and diagnostic endocrinology, vol I. North Holland, Amsterdam, pp 318–368

    Google Scholar 

  • Blaschko H, Comline RS, Schneider FH, Silver M, Smith AD (1967) Secretion of a chromaffin granule protein, chromogranin, from the adrenal gland after splanchnic stimulation. Nature 215:58–59

    Google Scholar 

  • Bosman FT (1983) Some recent developments in immunocytochemistry. Histochem J 15:189–200

    Google Scholar 

  • Cegrell L (1968) The occurrence of biogenic monoamines in the mammalian endocrine pancreas. Acta Physiol Scand Suppl 314:1–60

    Google Scholar 

  • Cohn DV, Zangerle R, Fischer-Colbric R, Chu LL, Elting JJ, Hamilton JW, Winkler H (1982) Similarity of secretory protein I from parathyroid gland to chromogranin A from adrenal medulla. Proc Natl Acad Sci USA 79:6056–6059

    Google Scholar 

  • Cohn DV, Elting JJ, Frick M, Elde R (1984) Selective localization of the parathyroid secretory protein-I/ adrenal medulla chromogranin A protein family in a wide varicty of endocrine cells of the rat. Endocrinology 114:1963–1974

    Google Scholar 

  • DeStephano DB, Lloyd RV, Pike AM, Wilson BS (1984) Pituitary adenomas. An immunohistochemical study of hormone production and chromogranin localization. Am J Pathol 116:464–472

    Google Scholar 

  • Douglas WW (1974) Involvement of calcium in exocytosis and the exocytosis vesiculation sequence. Biochem Soc Symp 39:1–28

    Google Scholar 

  • Ehrhart M, Grube D, Bader M-F, Aunis D, Gratzl M (1986) Chromogranin A in the pancreatic islet: cellular and subcellular distribution. J Histochem Cytochem (in press)

  • Erspamer V (1937) Cellule enterocromaffini e cellule argentofile nel pancreas dell'uomo e dei mammiferi. Z Anat Entwicklungsgesch 107:574–619

    Google Scholar 

  • Facer P, Bishop AE, Lloyd RV, Wilson BS, Hennessy RJ, Polak JM (1985) Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract. Gastroenterology 89:1366–1373

    Google Scholar 

  • Falck B, Hellman B (1963) Evidence for the presence of biogenic amines in pancreatic islets. Experientia 19:139–140

    Google Scholar 

  • Falck B, Hillarp N-Å, Thieme G, Torp A (1962) Fluorescence of catecholamines and related compounds condensed with formaldehyde. J Histochem Cytochem 10:348–354

    Google Scholar 

  • Falkensammer G, Fischer-Colbrie R, Richter K, Winkler H (1985) Cell-free and cellular synthesis of chromogranin A and B of bovine adrenal medulla. Neuroscience 14:735–746

    Google Scholar 

  • Fujita T (1977) Concept of paraneurons. Arch Histol Jpn 40 (Suppl):1–12

    Google Scholar 

  • Fujita T (1983) Messenger substances of neurons and paraneurons: their chemical nature and the routes and ranges of their transport to targets. Biomed Res 4:239–256

    Google Scholar 

  • Gorgas K, Böck P (1976) Morphology and histochemistry of the adrenal medulla. I. Various types of primary catecholaminestoring cells in the mouse adrenal medulla. Histochemistry 50:17–31

    Google Scholar 

  • Grube D (1976) Biogenic monoamines in the GEP endocrine system of various mammals. In: Fujita T (ed) Endocrine gut and pancreas. Elsevier, Amsterdam, pp 119–132

    Google Scholar 

  • Grube D (1980a) Immunoreactivities of gastrin (G-)-cells. II. Nonspecific binding of immunoglobulins to G-cells by ionic interactions. Histochemistry 66:149–167

    Google Scholar 

  • Grube D (1980b) Immunoperoxidase methods: increased efficiency using fluorescence microscopy for 3,3 diaminobenzidine (DAB) stained semithin sections. Histochemistry 70:19–22

    Google Scholar 

  • Grube D (1982) Die endokrinen Zellen des Verdauungsapparats. Klin Wochenschr 60:213–227

    Google Scholar 

  • Grube D (1986) The endocrine cells of the digestive system: amines, peptides, and modes of action. Anat Embryol (in press)

  • Grube D, Aebert H (1981) Immunocytochemical investigations of GEP endocrine cells using semithin and ultrathin serial sections. In: Grossman MI, Brazier MAB, Lechago J (eds) Cellular basis of chemical messengers in the digestive system. Academic Press, New York, pp 83–95

    Google Scholar 

  • Grube D, Bohn R (1983) The microanatomy of human islets of Langerhans, with special reference to somatostatin (D-) cells. Arch Histol Jpn 46:327–353

    Google Scholar 

  • Grube D, Eckert I, Speck PT, Wagner H-J (1983) Immunohistochemistry and microanatomy of the islets of Langerhans. Biomed Res 4 (Suppl):25–36

    Google Scholar 

  • Hogue Angeletti R, Hickey WF (1985) A neuroendocrine marker in tissues of the immune system. Science 230:89–90

    Google Scholar 

  • Hutton JC, Penn EJ, Peshavaria M (1982) Isolation and characterization of insulin secretory granules from a rat islet cell tumour. Diabetologia 23:365–373

    Google Scholar 

  • Hutton JC, Hansen F, Peshavaria M (1985) β-granins:21kDa cosecreted peptides of the insulin granule closely related to adrenal medullary chromogranin A. FEBS Lett 188:336–340

    Google Scholar 

  • Kruggel W, O'Connor DT, Lewis RV (1985) The amino terminal sequence of bovine and human chromogranin A and secretory protein I are identical. Biochem Biophys Res Commun 127:380–383

    Google Scholar 

  • Lloyd RV, Wilson BS (1983) Specific endocrine tissue marker defined by a monoclonal antibody. Science 222:628–630

    Google Scholar 

  • Lloyd RV, Mervak T, Schmidt K, Warner TFCS, Wilson BS (1984) Immunohistochemical detection of chromogranin and neuronspecific enolase in pancreatic endocrine neoplasms. Am J Surg Pathol 8:607–614

    Google Scholar 

  • Lloyd RV, Wilson BS, Kovacs K, Ryan N (1985) Immunohistochemical localization of chromogranin in human hypophyses and pituitary adenomas. Arch Pathol Lab Med 109:515–517

    Google Scholar 

  • Nolan JA, Trojanowski JQ, Hogue Angeletti R (1985) Neurons and neuroendocrine cells contain chromogranin. Detection of the molecule in normal bovine tissues by immunochemical and immunohistochemical methods. J Histochem Cytochem 33:791–798

    Google Scholar 

  • O'Connor DT (1983) Chromogranin: widespread immunoreactivity in polypeptide hormone producing tissues and in serum Regul Peptides 6:263–280

    Google Scholar 

  • O'Connor DT, Burton D, Deftos LJ (1983a) Chromogranin A: immunohistology reveals its universal occurrence in normal polypeptide hormone producing endocrine glands. Life Sci 33:1657–1663

    Google Scholar 

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

    Google Scholar 

  • O'Connor DT, Burton DW, Parmer RJ, Deftos LJ (1984a) Human chromogranin A: detection by immunohistochemistry in C cells and diverse polypeptide hormone producing tumors. In: Cohn DV, Fujita T, Potts JT, Talmage RV (eds) Endocrine control of bone and calcium metabolism. Elsevier, Amsterdam, pp 187–190

    Google Scholar 

  • O'Connor DT, Frigon RP, Sokoloff RL (1984b) Human chromogranin A. Purification and characterization from catecholamine storage vesicles of human pheochromocytoma. Hypertension 6:2–12

    Google Scholar 

  • Pearse AGE (1969) The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem 17:303–313

    Google Scholar 

  • Pearse AGE (1980) APUD: concept, tumours, molecular markers and amyloid. Mikroskopie 36:257–269

    Google Scholar 

  • Pearse AGE, Polak JM (1975)Bifunctional reagents as yapour-and liquidphase fixatives for immunohistochemistry. Histochem J 7:179–186

    Google Scholar 

  • Petrusz P (1983) Essential requirements for the validity of immunocytochemical staining procedures. J Histochem Cytochem 31 (1 A Suppl):177–179

    Google Scholar 

  • Petrusz P, Ordronneau P, Finley CW (1980) Criteria of reliability for light microscopic immunocytochemical staining. Histochem J 12:333–348

    Google Scholar 

  • Reiffen FU, Gratzl M (1986) Chromogranins, widespread in endocrine and nervous tissue, bind Ca++. FEBS Lett 195:327–330

    Google Scholar 

  • Rosa P, Hille A, Lee RWH, Zanini A, De Camilli P, Huttner WB (1985) Secretogranins I and II: two tyrosinesulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway. J Cell Biol 101:1999–2011

    Google Scholar 

  • Serck-Hanssen G, O'Connor DT (1984) Immunological identification and characterization of chromogranins coded by poly(A)mRNA from bovine adrenal medulla and pituitary gland and human phaeochromocytoma. J Biol Chem 259:11597–11600

    Google Scholar 

  • Settleman J, Fonseca R, Nolan J, Hogue Angeletti R (1985) Relationship of multiple forms of chromogranin. J Biol Chem 260:1645–1651

    Google Scholar 

  • Solcia E, Creutzfeldt W, Falkmer S, Fujita T, Greider MH, Grube D, Håkanson R, Larsson L-I, Lechago J, Lewin K, Polak JM, Rubin W, Grossman MI (1981) Human gastroentero-pancreatic endocrine-paracrine cells: Santa Monica 1980 classification. In: Grossman MI, Brazier MAB, Lechago J (eds) Cellular basis of chemical messengers in the digestive system. Academic Press, New York, pp 159–165

    Google Scholar 

  • Somogyi P, Hodgson AJ, DePotter RW, Fischer-Colbrie R, Schober M, Winkler H, Chubb JW (1984) Chromogranin immunoreactivity in the central nervous system. Immunochemical characterisation, distribution and relationship to catecholamine and enkephalin pathways. Brain Res Rev 8:193–230

    Google Scholar 

  • Sopwith AM, Hales CN, Hutton JC (1984) Pancreatic B-cells secrete a range of novel peptides besides insulin. Biochim Biophys Acta 803:342–345

    Google Scholar 

  • Sternberger LA (1979) Immunocytochemistry, 2nd edn. J Wiley, New York

    Google Scholar 

  • Sternberger LA (1986) Immunocytochemistry.3rd edn. J Wiley, New York

    Google Scholar 

  • Van Noorden S, Polak JM (1983) Immunocytochemistry today. Techniques and practice. In: Van Noorden S, Polak JM (eds) Immunocytochemistry: applications in pathology and biology. J Wright & Sons, London, pp 11–42

    Google Scholar 

  • Varndell JM, Lloyd RV, Wilson BS, Polak JM (1985) Ultrastructural localization of chromogranin: potential marker for the electron microscopical recognition of endocrine cell secretory granules. Histochem J 17:981–992

    Google Scholar 

  • Wallis M, Howell SL, Taylor KW (1986) The biochemistry of the polypeptide hormones. J Wiley, New York

    Google Scholar 

  • Winkler H, Carmichael SW (1982) The chromaffin granule. In: Posner AM, Trifaro JM (eds) The secretory granule. Elsevier, Amsterdam New York, pp 4–79

    Google Scholar 

  • Winkler H, Hörtnagl H (1973) Composition and molecular organisation of chromaffin granules. Front Catecholamine Res 1973:415–421

    Google Scholar 

  • Wilson BS, Lloyd RV (1984) Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol 115:458–468

    Google Scholar 

  • Yoshie S, Aunis D, Bader F, Grube D (1987) Chromogranin A (CGA) in the gastro-entero-pancreatic (GEP) endocrine system. II. CGA and glucagon in human pancreatic A-cells (in prepration)

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grube, D., Aunis, D., Bader, F. et al. Chromogranin A (CGA) in the gastro-entero-pancreatic (GEP) endocrine system. Histochemistry 85, 441–452 (1986). https://doi.org/10.1007/BF00508425

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00508425

Keywords

Navigation