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. 1971 Aug 1;50(2):399–415. doi: 10.1083/jcb.50.2.399

ELECTRON MICROSCOPE RADIOAUTOGRAPHIC IDENTIFICATION OF SEROTONIN-SYNTHESIZING CELLS IN THE MOUSE GASTRIC MUCOSA

Walter Rubin 1, Michael D Gershon 1, Leonard L Ross 1
PMCID: PMC2108276  PMID: 5315585

Abstract

This study correlates the fine structure of mouse gastric endocrine cells with their ability to synthesize serotonin (5-HT) from 5-hydroxytryptophan (5-HTP). Mice were sacrificed 2 hr after the intravenous injection of 5-HTP-3H or 5-HT-3H. Their stomachs were processed for light- and electron microscope radioautography in a manner which retained labeled 5-HT while washing out other labeled substances. Stomachs from additional mice were incubated in vitro with 5-HT-3H and processed similarly. All morphologic types of mouse gastric endocrine cells exhibited a similar facility to incorporate exogenous 5-HTP and to convert it to 5-HT which was bound intracellularly. Differences in densities of silver grains observed over endocrine cells suggested that individual endocrine cells indeed varied in their ability to synthesize and/or to bind 5-HT; such variations, however, were not reflected by differences in fine structure, with the exception that endocrine cells with few granules always contained little newly synthesized 5-HT. The newly synthesized 5-HT was associated with the intracellular granules. The gastric endocrine cells were not labeled by exogenous 5-HT-3H, whereas mast cells were labeled by either 5-HT-3H or 5-HTP-3H administration. The findings of the present study support the position that the gastric endocrine cells represent a single cell type, at least in respect to serotonin metabolism—that the argyrophil or argentaffin reactivity of these cells merely reflects their amine content at a given time.

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Selected References

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  1. BAKER R. V. Observations on the localization of 5-hydroxytryptamine. J Physiol. 1958 Aug 6;142(3):563–570. doi: 10.1113/jphysiol.1958.sp006036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BULBRING E., LIN R. C. The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis; the local production of 5-HT and its release in relation to intraluminal pressure and propulsive activity. J Physiol. 1958 Mar 11;140(3):381–407. [PMC free article] [PubMed] [Google Scholar]
  3. Bussolati G., Pearse A. G. Immunofluorescent localization of the gastrin-secreting G cells in the pyloric antrum of the pig. Histochemie. 1970;21(1):1–4. doi: 10.1007/BF00304798. [DOI] [PubMed] [Google Scholar]
  4. Carvalheira A. F., Welsch U., Pearse A. G. Cytochemical and ultrastructural observations on the argentaffin and argyrophil cells of the gastro-intestinal tract in mammals, and their place in the APUD series of polypeptide-secreting cells. Histochemie. 1968;14(1):33–46. doi: 10.1007/BF00268031. [DOI] [PubMed] [Google Scholar]
  5. ERSPAMER V., ASERO B. Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5-hydroxytryptamine. Nature. 1952 May 10;169(4306):800–801. doi: 10.1038/169800b0. [DOI] [PubMed] [Google Scholar]
  6. Forssmann W. G., Orci L., Pictet R., Renold A. E., Rouiller C. The endocrine cells in the epithelium of the gastrointestinal mucosa of the rat. An electron microscope study. J Cell Biol. 1969 Mar;40(3):692–715. doi: 10.1083/jcb.40.3.692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gershon M. D., Ross L. L. Location of sites of 5-hydroxytryptamine storage and metabolism by radioautography. J Physiol. 1966 Oct;186(2):477–492. doi: 10.1113/jphysiol.1966.sp008047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gershon M. D., Ross L. L. Radioisotopic studies of the binding, exchange, and distribution of 5-hydroxytryptamine synthesized from its radioactive precursor. J Physiol. 1966 Oct;186(2):451–476. doi: 10.1113/jphysiol.1966.sp008046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. HAMPERL H. Uber argyrophile Zellen. Virchows Arch Pathol Anat Physiol Klin Med. 1952 Apr;321(5):482–507. [PubMed] [Google Scholar]
  10. Hammarström L., Ritzén M., Ullberg S. Combined autoradiography and fluorescence microscopy. Localization of labelled 5-hydroxytryptophan in relation to endogenous 5-hydroxytryptamine in the gastrointestinal tract. Experientia. 1966 Apr 15;22(4):213–215. doi: 10.1007/BF01900913. [DOI] [PubMed] [Google Scholar]
  11. Håkanson R., Lilja B., Owman C. Properties of a new system of amine-storing cells in the gastric mucosa of the rat. Eur J Pharmacol. 1967 May;1(3):188–199. doi: 10.1016/0014-2999(67)90004-0. [DOI] [PubMed] [Google Scholar]
  12. Håkanson R., Owman C. Concomitant histochemical demonstration of histamine and catecholamines in enterochromaffin-like cells of gastric mucosa. Life Sci. 1967 Apr 1;6(7):759–766. doi: 10.1016/0024-3205(67)90133-6. [DOI] [PubMed] [Google Scholar]
  13. Håkanson R., Owman C. Distribution and properties of amino acid decarboxylases in gastric mucosa. Biochem Pharmacol. 1966 Apr;15(4):489–499. doi: 10.1016/0006-2952(66)90259-0. [DOI] [PubMed] [Google Scholar]
  14. Håkanson R., Owman C., Sjöberg N. O., Sporrong B. Amine mechanisms in enterochromaffin and enterochromaffin-like cells of gastric mucosa in various mammals. Histochemie. 1970;21(3):189–220. doi: 10.1007/BF00304213. [DOI] [PubMed] [Google Scholar]
  15. ITO S., WINCHESTER R. J. The fine structure of the gastric mucosa in the bat. J Cell Biol. 1963 Mar;16:541–577. doi: 10.1083/jcb.16.3.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. LOVENBERG W., WEISSBACH H., UDENFRIEND S. Aromatic L-amino acid decarboxylase. J Biol Chem. 1962 Jan;237:89–93. [PubMed] [Google Scholar]
  17. LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laduron P., Belpaire F. Tissue fractionation and catecholamines. II. Intracellular distribution patterns of tyrosine hydroxylase, dopa decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine N-methyltransferase and monoamine oxidase in adrenal medulla. Biochem Pharmacol. 1968 Jul;17(7):1127–1140. doi: 10.1016/0006-2952(68)90048-8. [DOI] [PubMed] [Google Scholar]
  19. McGuigan J. E. Gastric mucosal intracellular localization of gastrin by immunofluorescence. Gastroenterology. 1968 Sep;55(3):315–327. [PubMed] [Google Scholar]
  20. Oates J. A., Butler T. C. Pharmacologic and endocrine aspects of carcinoid syndrome. Adv Pharmacol. 1967;5:109–128. doi: 10.1016/s1054-3589(08)60656-0. [DOI] [PubMed] [Google Scholar]
  21. Orci L., Pictet R., Forssmann W. G., Renold A. E., Rouiller C. Structural evidence for glucagon producing cells in the intestinal mucosa of the rat. Diabetologia. 1968 Jan;4(1):56–67. doi: 10.1007/BF01241034. [DOI] [PubMed] [Google Scholar]
  22. PALADE G. E. A study of fixation for electron microscopy. J Exp Med. 1952 Mar;95(3):285–298. doi: 10.1084/jem.95.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Penttilä A., Lempinen M. Enterochromaffin cells and 5-hydroxytryptamine in the human intestinal tract. Gastroenterology. 1968 Mar;54(3):375–381. [PubMed] [Google Scholar]
  24. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ratzenhofer M., Leb D. Uber die Feinstruktur der argentaffinen und der anderen Erscheinungsformen der "Hellen Zellen" Feyrter's im Kaninchen-Magen. Z Zellforsch Mikrosk Anat. 1965 Jul 5;67(1):113–150. [PubMed] [Google Scholar]
  26. Singh I. Argyrophile and argentaffin reactions in individual granules of enterochromaffin cells of reserpine treated guinea pigs. Z Zellforsch Mikrosk Anat. 1967;81(4):501–510. doi: 10.1007/BF00541011. [DOI] [PubMed] [Google Scholar]
  27. Snyder S. H., Axelrod J., Zweig M. A sensitive and specific fluorescence assay for tissue serotonin. Biochem Pharmacol. 1965 May;14(5):831–835. doi: 10.1016/0006-2952(65)90102-4. [DOI] [PubMed] [Google Scholar]
  28. Solcia E., Sampietro R. Cytologic observations on the pancreatic islets with reference to some endocrine-like cells of the gastrointestinal mucosa. Z Zellforsch Mikrosk Anat. 1965 Dec 10;68(5):689–698. doi: 10.1007/BF00340094. [DOI] [PubMed] [Google Scholar]
  29. Solcia E., Vassallo G., Capella C. Studies on the G cells of the pyloric mucosa, the probable site of gastrin secretion. Gut. 1969 May;10(5):379–388. doi: 10.1136/gut.10.5.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Solcia E., Vassallo G., Sampietro R. Endocrine cells in the antro-pyloric mucosa of the stomach. Z Zellforsch Mikrosk Anat. 1967;81(4):474–486. doi: 10.1007/BF00541009. [DOI] [PubMed] [Google Scholar]
  31. Stjärne L. Storage particles in noradrenergic tissues. Pharmacol Rev. 1966 Mar;18(1):425–432. [PubMed] [Google Scholar]
  32. TRUMP B. F., SMUCKLER E. A., BENDITT E. P. A method for staining epoxy sections for light microscopy. J Ultrastruct Res. 1961 Aug;5:343–348. doi: 10.1016/s0022-5320(61)80011-7. [DOI] [PubMed] [Google Scholar]
  33. Thunberg R. Localization of cells containing and forming histamine in the gastric mucosa of the rat. Exp Cell Res. 1967 Aug;47(1):108–115. doi: 10.1016/0014-4827(67)90214-5. [DOI] [PubMed] [Google Scholar]
  34. UDENFRIEND S., WEISSBACH H., BOGDANSKI D. F. Effect of iproniazid on serotonin metabolism in vivo. J Pharmacol Exp Ther. 1957 Jun;120(2):255–260. [PubMed] [Google Scholar]
  35. UDENFRIEND S., WEISSBACH H., BOGDANSKI D. F. Increase in tissue serotonin following administration of its precursor 5-hydroxytryptophan. J Biol Chem. 1957 Feb;224(2):803–810. [PubMed] [Google Scholar]
  36. Vassallo G., Solcia E., Capella C. Light and electron microscopic identification of several types of endocrine cells in the gastrointestinal mucosa of the cat. Z Zellforsch Mikrosk Anat. 1969;98(3):333–356. doi: 10.1007/BF00346679. [DOI] [PubMed] [Google Scholar]
  37. Weiner N. Regulation of norepinephrine biosynthesis. Annu Rev Pharmacol. 1970;10:273–290. doi: 10.1146/annurev.pa.10.040170.001421. [DOI] [PubMed] [Google Scholar]
  38. Weinshelbaum E. I., Ferguson D. J. Localization of carbon-14 from histamine in enterochromaffin cells. Gastroenterology. 1966 Dec;51(6):1028–1036. [PubMed] [Google Scholar]

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