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. 1994 May-Aug;67(3-4):123–134.

The biology and physiology of the ECL cell.

R Håkanson 1, D Chen 1, K Andersson 1, H J Monstein 1, C M Zhao 1, B Ryberg 1, F Sundler 1, H Mattsson 1
PMCID: PMC2588926  PMID: 7502521

Abstract

The enterochromaffin-like (ECL) cells, which are the predominant endocrine cell type in the acid-producing part of the vertebrate stomach, are characterized by numerous, electron-lucent vesicles and few electron-dense granules in the cytoplasm. The biological and physiological significance of the ECL cells remains poorly understood. They produce and store histamine and pancreastatin and are thought to produce an as yet unidentified peptide hormone. The most important clue to their function is their willingness to respond to changes in circulating gastrin. The present review presents current knowledge of the biology and physiology of the rat stomach ECL cells. Examination of serially sectioned ECL cells has revealed that the cytoplasmic vesicles almost invariably contain an electron-dense core, suggesting that perhaps the distinction between granules and vesicles is artificial. We propose a life cycle of the secretory organelles in the ECL cells with a progressive development from granules to vesicles. The results showed that the gastrin-evoked release of histamine and pancreastatin was accompanied by loss of vesicles, and that synthesis of histamine and pancreastatin was accelerated by sustained infusion of gastrin, a treatment that was associated with renewal of vesicles. The events described are instrumental in bringing about a change in the "steady state" or "equilibrium" of the ECL cells, from a non-stimulated, resting state to a gastrin-stimulated, active state. This change is attained within six to eight hr. The next "steady state" change is that from "normal-sized" but active ECL cells to "hypertrophic" ECL cells. The increase in cell size is complete after about one week. The gastrin-evoked increase in the ECL cell self-replication rate is maximal after about 10 days, after which time there is a gradual return back to pre-stimulation values. The ECL cell density increases fairly slowly and does not reach maximum (four-fold increase) until after 20 weeks hypergastrinemia. The activity of the histamine-forming enzyme, histidine decarboxylase, is elevated by gastrin and remains elevated for as long as the gastrin stimulus is maintained (the longest time studied was 20 weeks). The physiological significance of the ECL cells is probably related to their capacity to produce and store histamine and an as yet unidentified peptide hormone. The ECL cells are thought to be the source of histamine necessary for the gastrin-evoked acid response. In addition, preliminary evidence suggests that the ECL cells and the anticipated ECL cell hormone play a role in bone formation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson K., Chen D., Håkanson R., Mattsson H., Sundler F. Enterochromaffin-like cells in the rat stomach: effect of alpha-fluoromethylhistidine-evoked histamine depletion. A chemical, histochemical and electron-microscopic study. Cell Tissue Res. 1992 Oct;270(1):7–13. doi: 10.1007/BF00381874. [DOI] [PubMed] [Google Scholar]
  2. Andersson K., Håkanson R., Mattsson H., Ryberg B., Sundler F. Hyperplasia of histamine-depleted enterochromaffinlike cells in rat stomach using omeprazole and alpha-fluoromethylhistidine. Gastroenterology. 1992 Sep;103(3):897–904. doi: 10.1016/0016-5085(92)90023-r. [DOI] [PubMed] [Google Scholar]
  3. Axelson J., Håkanson R., Rosengren E., Sundler F. Hypergastrinaemia induced by acid blockade evokes enterochromaffin-like (ECL) cell hyperplasia in chicken, hamster and guinea-pig stomach. Cell Tissue Res. 1988;254(3):511–516. doi: 10.1007/BF00226500. [DOI] [PubMed] [Google Scholar]
  4. Axelson J., Persson P., Gagnemo-Persson R., Håkanson R. Importance of the stomach in maintaining calcium homoeostasis in the rat. Gut. 1991 Nov;32(11):1298–1302. doi: 10.1136/gut.32.11.1298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Böttcher G., Håkanson R., Nilsson G., Seensalu R., Sundler F. Effects of long-term hypergastrinaemia on the ultrastructure of enterochromaffin-like cells in the stomach of the rat, hamster and guinea pig. Cell Tissue Res. 1989;256(2):247–257. doi: 10.1007/BF00218882. [DOI] [PubMed] [Google Scholar]
  6. Cetin Y., Grube D. Immunoreactivities for chromogranin A and B, and secretogranin II in the guinea pig entero-endocrine system: cellular distributions and intercellular heterogeneities. Cell Tissue Res. 1991 May;264(2):231–241. doi: 10.1007/BF00313960. [DOI] [PubMed] [Google Scholar]
  7. Cetin Y., Müller-Köppel L., Aunis D., Bader M. F., Grube D. Chromogranin A (CgA) in the gastro-entero-pancreatic (GEP) endocrine system. II. CgA in mammalian entero-endocrine cells. Histochemistry. 1989;92(4):265–275. doi: 10.1007/BF00500540. [DOI] [PubMed] [Google Scholar]
  8. Chen D., Monstein H. J., Nylander A. G., Zhao C. M., Sundler F., Håkanson R. Acute responses of rat stomach enterochromaffinlike cells to gastrin: secretory activation and adaptation. Gastroenterology. 1994 Jul;107(1):18–27. doi: 10.1016/0016-5085(94)90056-6. [DOI] [PubMed] [Google Scholar]
  9. Curry W. J., Johnston C. F., Shaw C., Buchanan K. D. Distribution and partial characterisation of immunoreactivity to the putative C-terminus of rat pancreastatin. Regul Pept. 1990 Oct 8;30(3):207–219. doi: 10.1016/0167-0115(90)90096-f. [DOI] [PubMed] [Google Scholar]
  10. Delwaide J., Vivario M., Belaïche J., Louis E., Courtoy R., Gast P., Boniver J. Ultrastructural demonstration of histamine in human enterochromaffin like cell granules. Gut. 1991 Jul;32(7):834–834. doi: 10.1136/gut.32.7.834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grube D., Bargsten G., Cetin Y., Yoshie S. Chromogranins in mammalian GEP endocrine cells: their distribution and interrelations with co-stored amines and peptides. Arch Histol Cytol. 1989;52 (Suppl):91–98. doi: 10.1679/aohc.52.suppl_91. [DOI] [PubMed] [Google Scholar]
  12. Håkanson R., Böttcher G., Ekblad E., Panula P., Simonsson M., Dohlsten M., Hallberg T., Sundler F. Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies. Histochemistry. 1986;86(1):5–17. doi: 10.1007/BF00492340. [DOI] [PubMed] [Google Scholar]
  13. Håkanson R., Böttcher G., Sundler F., Vallgren S. Activation and hyperplasia of gastrin and enterochromaffin-like cells in the stomach. Digestion. 1986;35 (Suppl 1):23–41. doi: 10.1159/000199380. [DOI] [PubMed] [Google Scholar]
  14. Håkanson R., Liedberg G. Effects of brocresine (NSD-1055) and cycloheximide on amino acid decarboxylase activities in gastric mucosa of normal and vagally denervated rats. Br J Pharmacol. 1972 Dec;46(4):688–695. doi: 10.1111/j.1476-5381.1972.tb06893.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Håkanson R., Owman C., Sporrong B., Sundler F. Electron microscopic classification of amine-producing endocrine cells by selective staining of ultra-thin sections. Histochemie. 1971;27(3):226–242. doi: 10.1007/BF00264395. [DOI] [PubMed] [Google Scholar]
  16. Håkanson R., Owman C., Sporrong B., Sundler F. Electron microscopic identification of the histamine-storing argyrophil (enterochromaffin-like) cells in the rat stomach. Z Zellforsch Mikrosk Anat. 1971;122(4):460–466. doi: 10.1007/BF00936080. [DOI] [PubMed] [Google Scholar]
  17. Håkanson R., Persson P., Axelson J., Johnell O., Sundler F. Evidence that gastrin enhances 45Ca uptake into bone through release of a gastric hormone. Regul Pept. 1990 Mar 27;28(1):107–118. doi: 10.1016/0167-0115(90)90068-8. [DOI] [PubMed] [Google Scholar]
  18. Håkanson R., Tielemans Y., Chen D., Andersson K., Mattsson H., Sundler F. Time-dependent changes in enterochromaffin-like cell kinetics in stomach of hypergastrinemic rats. Gastroenterology. 1993 Jul;105(1):15–21. doi: 10.1016/0016-5085(93)90005-w. [DOI] [PubMed] [Google Scholar]
  19. Kubota H., Taguchi Y., Tohyama M., Matsuura N., Shiosaka S., Ishihara T., Watanabe T., Shiotani Y., Wada H. Electron microscopic identification of histidine decarboxylase-containing endocrine cells of the rat gastric mucosa. An immunohistochemical analysis. Gastroenterology. 1984 Sep;87(3):496–502. [PubMed] [Google Scholar]
  20. Larsson H., Carlsson E., Håkanson R., Mattsson H., Nilsson G., Seensalu R., Wallmark B., Sundler F. Time-course of development and reversal of gastric endocrine cell hyperplasia after inhibition of acid secretion. Studies with omeprazole and ranitidine in intact and antrectomized rats. Gastroenterology. 1988 Dec;95(6):1477–1486. doi: 10.1016/s0016-5085(88)80066-0. [DOI] [PubMed] [Google Scholar]
  21. Larsson H., Carlsson E., Mattsson H., Lundell L., Sundler F., Sundell G., Wallmark B., Watanabe T., Håkanson R. Plasma gastrin and gastric enterochromaffinlike cell activation and proliferation. Studies with omeprazole and ranitidine in intact and antrectomized rats. Gastroenterology. 1986 Feb;90(2):391–399. doi: 10.1016/0016-5085(86)90938-8. [DOI] [PubMed] [Google Scholar]
  22. Nissinen M. J., Panula P. Histamine-storing cells in the oxyntic mucosa of the rat stomach: a transmission electron microscopic study employing fixation with carbodiimide. J Histochem Cytochem. 1993 Sep;41(9):1405–1412. doi: 10.1177/41.9.8354880. [DOI] [PubMed] [Google Scholar]
  23. Persson P., Gagnemo-Persson R., Chen D., Axelson J., Nylander A. G., Johnell O., Häkanson R. Gastrectomy causes bone loss in the rat: is lack of gastric acid responsible? Scand J Gastroenterol. 1993 Apr;28(4):301–306. doi: 10.3109/00365529309090245. [DOI] [PubMed] [Google Scholar]
  24. Persson P., Håkanson R., Axelson J., Sundler F. Gastrin releases a blood calcium-lowering peptide from the acid-producing part of the rat stomach. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2834–2838. doi: 10.1073/pnas.86.8.2834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Prinz C., Kajimura M., Scott D. R., Mercier F., Helander H. F., Sachs G. Histamine secretion from rat enterochromaffinlike cells. Gastroenterology. 1993 Aug;105(2):449–461. doi: 10.1016/0016-5085(93)90719-s. [DOI] [PubMed] [Google Scholar]
  26. Rindi G., Buffa R., Sessa F., Tortora O., Solcia E. Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Distribution, distinction from costored hormones/prohormones and relationship with the argyrophil component of secretory granules. Histochemistry. 1986;85(1):19–28. doi: 10.1007/BF00508649. [DOI] [PubMed] [Google Scholar]
  27. Rubin W., Schwartz B. An electron microscopic radioautographic identification of the "enterochromaffin-like" APUD cells in murine oxyntic glands. Demonstration of a metabolic difference between rat and mouse gastric A-like cells. Gastroenterology. 1979 Mar;76(3):437–449. [PubMed] [Google Scholar]
  28. Rubin W., Schwartz B. Electron microscopic radioautographic identification of the ECL cell as the histamine-synthesizing endocrine cell in the rat stomach. Gastroenterology. 1979 Sep;77(3):458–467. [PubMed] [Google Scholar]
  29. Rubin W., Schwartz B. Electron microscopic radioautographic identification of the ECL cell as the histamine-synthesizing endocrine cell in the rat stomach. Gastroenterology. 1979 Sep;77(3):458–467. [PubMed] [Google Scholar]
  30. Ryberg B., Axelson J., Håkanson R., Sundler F., Mattsson H. Trophic effects of continuous infusion of [Leu15]-gastrin-17 in the rat. Gastroenterology. 1990 Jan;98(1):33–38. doi: 10.1016/0016-5085(90)91287-g. [DOI] [PubMed] [Google Scholar]
  31. Ryberg B., Carlsson E., Håkanson R., Lundell L., Mattsson H., Sundler F. Effects of partial resection of acid-secreting mucosa on plasma gastrin and enterochromaffin-like cells in the rat stomach. Digestion. 1990;45(2):102–108. doi: 10.1159/000200230. [DOI] [PubMed] [Google Scholar]
  32. Ryberg B., Tielemans Y., Axelson J., Carlsson E., Håkanson R., Mattson H., Sundler F., Willems G. Gastrin stimulates the self-replication rate of enterochromaffinlike cells in the rat stomach. Effects of omeprazole, ranitidine, and gastrin-17 in intact and antrectomized rats. Gastroenterology. 1990 Oct;99(4):935–942. doi: 10.1016/0016-5085(90)90610-d. [DOI] [PubMed] [Google Scholar]
  33. Sandvik A. K., Waldum H. L., Kleveland P. M., Schulze Søgnen B. Gastrin produces an immediate and dose-dependent histamine release preceding acid secretion in the totally isolated, vascularly perfused rat stomach. Scand J Gastroenterol. 1987 Sep;22(7):803–808. doi: 10.3109/00365528708991918. [DOI] [PubMed] [Google Scholar]
  34. Schulak J. A., Kaplan E. L. The importance of the stomach in gastrin-induced hypocalcemia in the rat. Endocrinology. 1975 May;96(5):1217–1220. doi: 10.1210/endo-96-5-1217. [DOI] [PubMed] [Google Scholar]
  35. Solcia E., Capella C., Vassallo G., Buffa R. Endocrine cells of the gastric mucosa. Int Rev Cytol. 1975;42:223–286. doi: 10.1016/s0074-7696(08)60982-1. [DOI] [PubMed] [Google Scholar]
  36. Tielemans Y., Axelson J., Sundler F., Willems G., Håkanson R. Serum gastrin concentration affects the self replication rate of the enterochromaffin like cells in the rat stomach. Gut. 1990 Mar;31(3):274–278. doi: 10.1136/gut.31.3.274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tielemans Y., Chen D., Sundler F., Håkanson R., Willems G. Reversibility of the cell kinetic changes induced by omeprazole in the rat oxyntic mucosa. An autoradiographic study using tritiated thymidine. Scand J Gastroenterol. 1992;27(2):155–160. doi: 10.3109/00365529209165437. [DOI] [PubMed] [Google Scholar]
  38. Tielemans Y., Håkanson R., Sundler F., Willems G. Proliferation of enterochromaffinlike cells in omeprazole-treated hypergastrinemic rats. Gastroenterology. 1989 Mar;96(3):723–729. [PubMed] [Google Scholar]

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