Skip to main content
Log in

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

II. CgA in mammalian entero-endocrine cells

  • Published:
Histochemistry Aims and scope Submit manuscript

Summary

Chromogranin A (CgA) and related acidic proteins are widely distributed in the organism. They are also present in entero-endocrine cells and in other members of the paraneuron family. Therefore, CgA has been claimed as an universal marker of this cellular community. To yield precise data about the distribution of CgA in entero-endocrine cells, all segments of the gastro-intestinal tract of five mammalian species (man, cattle, pig, cat, guinea-pig) were investigated immunohistochemically for CgA. In serial semithin plastic sections, all CgA-immunoreactive endocrine cells were identified for resident amines or peptides. CgA could be found in ten hormonally identified endocrine cell types and in two or three other endocrine cell types. Entero-endocrine cells containing amines (histamine, serotonin) regularly exhibited CgA-immunoreactivities. In contrast, peptide-containing endocrine cells were largely heterogeneous: Their CgA-immunoreactivities varied among the species, among the gastro-intestinal segments, and even among the members of the same cell population. Hence, seen histochemically, CgA is no universal marker for entero-endocrine cells. Seen biochemically, the observed heterogeneities of CgA-immunoreactivities theoretically can be attributed to various factors (species-specificities of CgA, subclasses of chromogranins, processing of CgA or its proprotein). Most probably, these heterogeneities are caused by species- or cell-specific differences in the extent of processing of CgA. In addition, some findings point to certain interrelations between the processing or storage of CgA and resisdent peptides in the secretion granules of entero-endocrine cells.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Ali-Rachedi A, Varndell IM, Adrian TE, Gapp DA, Van Noorden S, Bloom SR, Polak JM (1984) Peptide YY (PYY) immunoreactivity is co-stored with glucagon-related immunoreactants in endocrine cells of the gut and pancreas. Histochemistry 80:487–491

    Google Scholar 

  • Bargsten G, Grube D, Forssmann WG, Winkler H (1988) Chromogranins and serotonin metabolism in entero-endocrine cells. Acta Endocrinol (Suppl) 287:29–30

    Google Scholar 

  • Bigbee JW, Kosek JC, Eng LF (1977) Effects of primary antiserum dilution on staining of ‘antigen-rich’ tissues with the peroxidase anti-peroxidase technique. J Histochem Cytochem 25:443–447

    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 

  • Buffa R, Marè P, Gini A, Salvadore M (1988) Chromogranins A and B and secretogranin II in hormonally identified endocrine cells of the gut and pancreas. Basic Appl Histochem 32:471–484

    Google Scholar 

  • Cetin Y, Grube D (1989) Chromogranin A (CGA) im entero-endokrinen System der Säuger. Anat Anz 168:55

    Google Scholar 

  • Childs GV, Unabia G, Ellison D (1986) Immunocytochemical studies on pituitary hormones with PAP, ABC, and immunogold techniques: evolution of technology to best fit the antigen. Am J Pathol 175:307–330

    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 variety of endocrine cells of the rat. Endocrinology 114:1963–1974

    Google Scholar 

  • Ehrhart M, Grube D, Bader MF, Aunis D, Gratzl M (1986) Chromogranin A in the pancreatic islet: cellular and subcellular distribution. J Histochem Cytochem 34:1673–1682

    Google Scholar 

  • Eiden LE (1987) Is chromogranin a prohormone? Nature 325: 301

    Google Scholar 

  • Eiden LE, Huttner WB, Mallet J, O'Connor DT, Winkler H, Zanini A (1987) A nomenclature proposal for the chromogranin/ secretogranin proteins. Neuroscience 21:1019–1021

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

    Google Scholar 

  • Fischer-Colbrie R, Lassmann H, Hagn C, Winkler H (1985) Immunological studies on the distribution of chromogranin A and B in endocrine and nervous tissue. Neuroscience 16:547–555

    Google Scholar 

  • Fischer-Colbrie R, Iacangelo A, Eiden LE (1988) Neural and humoral factors separately regulate neuropeptide Y, enkephalin, and chromogranin A and B mRNA levels in rat adrenal medulla. Proc Natl Acad Sci USA 85:3240–3244

    Google Scholar 

  • Fujita T, Kanno T, Kobayashi S (1988) The paraneuron. Springer, Tokyo

    Google Scholar 

  • Gosselin EJ, Cate CC, Pettengill OS, Sorenson GD (1986) Immunocytochemistry: its evolution and criteria for its application in the study of epon-embedded cells and tissue. Am J Anat 175:135–160

    Google Scholar 

  • Grimelius L (1969) A silver nitrate stain for α2 cells in human panereatic islets. Acta Soc Med Upsal 73:243–270

    Google Scholar 

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

    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 175:151–162

    Google Scholar 

  • Grube D, Kusumoto Y (1986) Serial semithin sections in immunohistochemistry: techniques and applications. Arch Histol Jpn 49:391–410

    Google Scholar 

  • Grube D, Weber E (1980) Immunoreactivities of gastrin (G-) cells. I. Dilution-dependent staining of G-cells by antisera and nonimmune sera. Histochemistry 65:223–237

    Google Scholar 

  • Grube D, Yoshie S (1989) Immunohistochemistry of chromogranins A and B and secretogranin II in the canine endocrine pancreas. Arch Histol Cytol (in press)

  • Grube D, Aunis A, Bader F, Cetin Y, Jörns A, Yoshie S (1986) Chromogranin A (CGA) in the gastro-entero-pancreatic (GEP) endocrine system. I. CGA in the mammalian endocrine pancreas. Histochemistry 85:441–452

    Google Scholar 

  • Grube D, Bargsten G, Cetin Y, Jörns A, Yoshie S (1989a) Chromogranine in den endokrinen Zellen des Verdauungsapparats. Acta Histochem (in press)

  • Grube D, Bargsten G, Cetin Y, Yoshie S (1989b) Chromogranins in mammalian GEP endocrone cells: distribution and interrelations with costored amines and peptides. Arch Histol Cytol (Suppl) (in press)

  • Hagn C, Schmid KW, Fischer-Colbrie R, Winkler H (1986) Chromogranin A, B and C in human adrenal medulla and endocrine tissues. Lab Invest 55:405–411

    Google Scholar 

  • Håkanson R, Böttcher G, Ekblad E, Panula P, Simonsson M, Dohlsten M, Hallberg T, Sundler F (1986) Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies. Histochemistry 86:5–17

    Google Scholar 

  • Helmstaedter V, Taugner C, Feurle GE, Forssmann WG (1977) Localization of neurotensin-immunoreactive cells in the small intestine of man and various mammals. Histochemistry 53:35–41

    Google Scholar 

  • Helmstaedter V, Kreppein W, Domschke W, Mitznegg P, Yanaihara N, Wünsch E, Forssmann WG (1979) Immunohistochemical localization of motilin in endocrine non-enterochromaffin cells of the small intestine of humans and monkey. Gastroenterology 76:897–902

    Google Scholar 

  • Huttner WB, Benedum UM (1987) Chromogranin A and pancreastatin. Nature 325:305

    Google Scholar 

  • Hutton JC, Davidson HW, Peshavaria M (1987a) Proteolytic processing of chromogranin A in purified insulin granules. Biochem J 244:457–464

    Google Scholar 

  • Hutton JC, Davidson HW, Peshavaria M (1987b) The mechanism of chromogranin A processing. Nature 325:766

    Google Scholar 

  • Iacangelo A, Affolter HU, Eiden LE, Herbert E, Grimes M (1986) Bovine chromogranin A: its sequence and the distribution of its messenger RNA in endocrine tissues. Nature 323:82–86

    Google Scholar 

  • Konecki DS, Benedum UM, Gerdes HH, Huttner WB (1987) The primary structure of human chromogranin A and pancreastatin. J Biol Chem 262:17026–17030

    Google Scholar 

  • Larsson L-I (1983) Methods for immunocytochemistry of neurohormonal peptides. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy. Elsevier, Amsterdam, pp 147–209

    Google Scholar 

  • Lassmann H, Hagn C, Fischer-Colbrie R, Winkler H (1986) Presence of chromogranin A, B and C in bovine endocrine and nervous tissues: a comparative immunohistochemical study. Histochem J 18:380–386

    Google Scholar 

  • Pearse AGE, Polak JM, Adams C, Kendall PA (1974) Diethylpyrocarbonate, a vapour-phase fixative for immunofluorescence studies on polypeptide hormones. Histochem J 6:347–352

    Google Scholar 

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

    Google Scholar 

  • Polak JM, Bloom SR, Kusio M, Brown JC, Pearse AGE (1973) Cellular localisation of gastric inhibitory polypeptide in the duodenum and jejunum. Gut 14:284–288

    Google Scholar 

  • Ravazzola M, Orci L (1980) A pancreatic polypeptide (PP)-like immunoreactant is present in the glicentin-containing cell of the cat intestine. Histochemistry 67:221–224

    Google Scholar 

  • Rieker S, Fischer-Colbrie R, Eiden L, Winkler H (1988) Phylogenetic distribution of peptides related to chromogranins A and B. J Neurochem 50:1066–1073

    Google Scholar 

  • Rindi G, Buffa R, Sessa F, Tortora O, Solcia E (1986) Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Histochemistry 85:19–28

    Google Scholar 

  • Schlegel W, Raptis S (1976) A reliable method for generating antibodies against pancreozymin, secretin and gastrin. Clin Chim Acta 73:439–444

    Google Scholar 

  • Schlegel W, Raptis S, Grube D, Pfeiffer EF (1977) Estimation of cholecystokinin-pancreozymin CCK in human plasma and tissue by a specific radioimmunoassay and the immunohistochemical identification of pancreozymin-producing cells in the duodenum of humans. Clin Chim Acta 80:305–316

    Google Scholar 

  • Schmidt WE, Siegel EG, Lamberts R, Gallwitz B, Creutzfeldt W (1988) Pancreastatin: molecular and immunocytochemical characterization of a novel peptide in porcine and human tissues. Endocrinology 123:1395–1404

    Google Scholar 

  • Scopsi L, Wang B-L, Larsson L-I (1986) Nonspecific immunocytochemical reactions with certain neurohormonal peptides and basic peptide sequences. J Histochem Cytochem 34:1469–1475

    Google Scholar 

  • Shimizu F, Ikei N, Iwanaga T, Fujita T (1987) An immunochemical and immunohistochemical study on pancreastatin-like immunoreactivity using synthetic peptides. Biomed Res 8:457–462

    Google Scholar 

  • Simon J-P, Aunis D (1989) Biochemistry of the chromogranin A protein family. Biochem J (in press)

  • Simon J-P, Bader M-F, Aunis D (1988) Secretion from chromaffin cells is controlled by chromogranin A-derived peptides. Proc Natl Acad Sci USA 85:1712–1716

    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 

  • Solcia E, Capella C, Buffa R, Usellini L, Fiocca R, Sessa F (1987) Endocrine cells of the digestive system. In: Johnson LR (ed) Physiology of the gastrointestinal tract, 2nd edn. Raven Press, New York, pp 111–130

    Google Scholar 

  • Sternberger LA (1986) Immunohistochemistry, 3rd edn. John Wiley, New York

    Google Scholar 

  • Tatemoto K, Efendic S, Mutt V, Makk G, Feistner GJ, Barchas JD (1986) Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 324:476–478

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

    Google Scholar 

  • Waschek JA, Pruss RM, Siegel RE, Eiden LE, Bader MF, Aunis D (1987) Regulation of enkephalin. VIP, and chromogranin biosynthesis in actively secreting chromaffin cells — multiple strategies for multiple peptides. Ann NY Acad Sci 493:308–323

    Google Scholar 

  • Wiedenamann B, Waldherr R, Buhr H, Hille A, Rosa P, Huttner WB (1988) Identification of gastroenteropancreatic neuroendocrine cells in normal and neoplastic human tissue with antibodies against synaptophysin, chromogranin A, secretogranin I (chromogranin B), and secretogranin II. Gastroenterology 95:1364–1374

    Google Scholar 

  • Winkler H, Apps DK, Fischer-Colbrie R (1986) The molecular function of adrenal chromaffin granules: established facts and unresolved topics. Neuroscience 18:261–290

    Google Scholar 

  • Wohlfarter T, Fischer-Colbrie R, Hogue-Angeletti R, Eiden LE, Winkler H (1988) Processing of chromogranin A within chromaffin granules starts at C- and N-terminal cleavage sites. FEBS Lett 231:67–70

    Google Scholar 

  • Yoshie S, Hagn C, Ehrhart M, Fischer-Colbrie R, Grube D, Winkler H, Gratzl M (1987) Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet. Histochemistry 87:99–106

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cetin, Y., Müller-Köppel, L., Aunis, D. et al. Chromogranin A (CgA) in the gastro-entero-pancreatic (GEP) endocrine system. Histochemistry 92, 265–275 (1989). https://doi.org/10.1007/BF00500540

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00500540

Keywords

Navigation