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. 1994 Nov;35(11):1547–1550. doi: 10.1136/gut.35.11.1547

Evaluation of the trophic effect of longterm treatment with the histamine H2 receptor antagonist loxtidine on rat oxyntic mucosa by differential counting of dispersed cells.

E Brenna 1, H G Swarts 1, C H Klaassen 1, J J de Pont 1, H L Waldum 1
PMCID: PMC1375609  PMID: 7828970

Abstract

To evaluate whether the general trophic effect of gastrin on the oxyntic mucosa is an indirect effect mediated by histamine H2 receptors, sustained 24 hour hypergastrinaemia was induced in Sprague-Dawley rats by treatment with the long acting and potent histamine H2 antagonist loxtidine for five months. The trophic effect was assessed by weight, enumeration of total mucosal cells, parietal cells, and enterochromaffin like cells in smears stained for the actual cells after enzymatic dispersion of the mucosa, and by biochemical analysis of oxyntic mucosal homogenates. The weight of the whole stomach and the oxyntic mucosa increased by 12.7% (p = 0.016) and 27.5% (p = 0.006), respectively. Total oxyntic mucosal protein content increased by 28.7% (p = 0.058). Total numbers of mucosal cells and parietal cells increased by 11.9% (NS) and 24.1% (NS), respectively. The amount of the parietal cell specific enzyme H+,K(+)-ATPase was unchanged. On the other hand, the number of enterochromaffin like cells and related parameters, histidine decarboxylase activity and histamine content of the oxyntic mucosa, showed a pronounced and significant increase. It is concluded that the general trophic effect of gastrin on the oxyntic mucosa is not mediated by the histamine H2 receptor. The tropic effect of gastrin on the parietal cell seems, in contrast with that on the enterochromaffin like cell, not to be specific but only reflecting the general trophic effect on the oxyntic mucosa.

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Selected References

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  1. 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]
  2. Beaven M. A., Wilcox G., Terpstra G. K. A microprocedure for the measurement of 14CO2 release from [14C]carboxyl-labeled amino acids. Anal Biochem. 1978 Feb;84(2):638–641. doi: 10.1016/0003-2697(78)90089-1. [DOI] [PubMed] [Google Scholar]
  3. Brenna E., Waldum H. L., Sandvik A. K., Schulze Søgnen B., Kristensen A. Effects on the rat oxyntic mucosa of the histamine2-antagonist loxtidine and the H+, K(+)-ATPase inhibitor omeprazole. Aliment Pharmacol Ther. 1992 Jun;6(3):335–349. doi: 10.1111/j.1365-2036.1992.tb00055.x. [DOI] [PubMed] [Google Scholar]
  4. Brenna E., Waldum H. L. Studies of isolated parietal and enterochromaffin-like cells from the rat. Scand J Gastroenterol. 1991 Dec;26(12):1295–1306. doi: 10.3109/00365529108998627. [DOI] [PubMed] [Google Scholar]
  5. Brittain R. T., Jack D., Reeves J. J., Stables R. Pharmacological basis for the induction of gastric carcinoid tumours in the rat by loxtidine, an insurmountable histamine H2-receptor blocking drug. Br J Pharmacol. 1985 Aug;85(4):843–847. doi: 10.1111/j.1476-5381.1985.tb11083.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CARD W. I., MARKS I. N. The relationship between the acid output of the stomach following "maximal" histamine stimulation and the parietal cell mass. Clin Sci. 1960 Feb;19:147–163. [PubMed] [Google Scholar]
  7. Crean G. P., Marshall M. W., Rumsey R. D. Parietal cell hyperplasia induced by the administration of pentagastrin (ICI 50,123) to rats. Gastroenterology. 1969 Aug;57(2):147–155. [PubMed] [Google Scholar]
  8. Creutzfeldt W., Stöckmann F., Conlon J. M., Fölsch U. R., Bonatz G., Wülfrath M. Effect of short- and long-term feeding of omeprazole on rat gastric endocrine cells. Digestion. 1986;35 (Suppl 1):84–97. doi: 10.1159/000199384. [DOI] [PubMed] [Google Scholar]
  9. Dimaline R., Sandvik A. K. Histidine decarboxylase gene expression in rat fundus is regulated by gastrin. FEBS Lett. 1991 Apr 9;281(1-2):20–22. doi: 10.1016/0014-5793(91)80348-7. [DOI] [PubMed] [Google Scholar]
  10. Ekman L., Hansson E., Havu N., Carlsson E., Lundberg C. Toxicological studies on omeprazole. Scand J Gastroenterol Suppl. 1985;108:53–69. [PubMed] [Google Scholar]
  11. Helander H. F., Rutgersson K., Helander K. G., Pisegna J. P., Gardner J. D., Jensen R. T., Maton P. N. Stereologic investigations of human gastric mucosa. II. Oxyntic mucosa from patients with Zollinger-Ellison syndrome. Scand J Gastroenterol. 1992 Oct;27(10):875–883. doi: 10.3109/00365529209000157. [DOI] [PubMed] [Google Scholar]
  12. Hogben C. A., Kent T. H., Woodward P. A., Sill A. J. Quantitative histology of the gastric mucosa: man, dog, cat, guinea pig, and frog. Gastroenterology. 1974 Dec;67(6):1143–1154. [PubMed] [Google Scholar]
  13. Håkanson R., Blom H., Carlsson E., Larsson H., Ryberg B., Sundler F. Hypergastrinaemia produces trophic effects in stomach but not in pancreas and intestines. Regul Pept. 1986 Feb;13(3-4):225–233. doi: 10.1016/0167-0115(86)90041-8. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. KAHLSON G., ROSENGREN E., SVAHN D., THUNBERG R. MOBILIZATION AND FORMATION OF HISTAMINE IN THE GASTRIC MUCOSA AS RELATED TO ACID SECRETION. J Physiol. 1964 Nov;174:400–416. doi: 10.1113/jphysiol.1964.sp007494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kleveland P. M., Haugen S. E., Waldum H. L. The preparation of bioactive 125I-gastrin, using Iodo-gen as oxidizing agent, and the use of this tracer in receptor studies. Scand J Gastroenterol. 1985 Jun;20(5):569–576. doi: 10.3109/00365528509089698. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Lewin M., Cheret A. M., Soumarmon A., Girodet J. Méthode pour l'isolement et le tri des cellules de la muqueuse fundique de rat. Biol Gastroenterol (Paris) 1974 Apr-May;7(2):139–144. [PubMed] [Google Scholar]
  19. MARKS I. N., KOMAROV S. A., SHAY H. Acid secretory responses to histamine and the parietal cell mass in the dog. Am J Physiol. 1958 Nov;195(2):528–534. doi: 10.1152/ajplegacy.1958.195.2.528. [DOI] [PubMed] [Google Scholar]
  20. Makhlouf G. M., McManus J. P., Card W. I. Action of the pentapeptide (ICI 50123) on gastric secretion in man. Gastroenterology. 1966 Oct;51(4):455–465. [PubMed] [Google Scholar]
  21. Modlin I. M., Zucker K. A., Zdon M. J., Sussman J., Adrian T. E. Characteristics of the spontaneous gastric endocrine tumor of mastomys. J Surg Res. 1988 Mar;44(3):205–215. doi: 10.1016/0022-4804(88)90049-2. [DOI] [PubMed] [Google Scholar]
  22. Morel A. M., Delaage M. A. Immunoanalysis of histamine through a novel chemical derivatization. J Allergy Clin Immunol. 1988 Oct;82(4):646–654. doi: 10.1016/0091-6749(88)90978-5. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Smolka A., Weinstein W. M. Immunoassay of pig and human gastric proton pump. Gastroenterology. 1986 Mar;90(3):532–539. doi: 10.1016/0016-5085(86)91105-4. [DOI] [PubMed] [Google Scholar]
  25. Streett C. S., Cimprich R. E., Robertson J. L. Pathologic findings in the stomachs of rats treated with the H2-receptor antagonist tiotidine. Scand J Gastroenterol Suppl. 1984;101:109–117. [PubMed] [Google Scholar]
  26. Swarovsky B., Eissele R., Gross M., Körtner G., Koop H., Arnold R., Simon B. Expression of the gastric H+/K(+)-ATPase and histidine decarboxylase during omeprazole treatment. Digestion. 1994;55(2):97–102. doi: 10.1159/000201132. [DOI] [PubMed] [Google Scholar]
  27. Swarts H. G., Van Uem T. J., Hoving S., Fransen J. A., De Pont J. J. Effect of free fatty acids and detergents on H,K-ATPase. The steady-state ATP phosphorylation level and the orientation of the enzyme in membrane preparations. Biochim Biophys Acta. 1991 Dec 9;1070(2):283–292. doi: 10.1016/0005-2736(91)90068-j. [DOI] [PubMed] [Google Scholar]
  28. Tari A., Yamamoto G., Sumii K., Sumii M., Takehara Y., Haruma K., Kajiyama G., Wu V., Sachs G., Walsh J. H. Role of histamine2 receptor in increased expression of rat gastric H(+)-K(+)-ATPase alpha-subunit induced by omeprazole. Am J Physiol. 1993 Oct;265(4 Pt 1):G752–G758. doi: 10.1152/ajpgi.1993.265.4.G752. [DOI] [PubMed] [Google Scholar]
  29. Van Uem T. J., Peters W. H., De Pont J. J. A monoclonal antibody against pig gastric H+/K(+)-ATPase, which binds to the cytosolic E1.K+ form. Biochim Biophys Acta. 1990 Mar 30;1023(1):56–62. doi: 10.1016/0005-2736(90)90009-d. [DOI] [PubMed] [Google Scholar]
  30. Waldum H. L., Brenna E., Sandvik A. K., Kleveland P. M., Petersen H., Søgnen B. Histamine and gastrin in plasma of patients with upper gastrointestinal diseases. Digestion. 1989;42(3):121–127. doi: 10.1159/000199836. [DOI] [PubMed] [Google Scholar]
  31. Waldum H. L., Brenna E., Sandvik A. K., Petersen H. Trophic effect of histamine on the stomach. Scand J Gastroenterol Suppl. 1991;180:137–142. doi: 10.3109/00365529109093191. [DOI] [PubMed] [Google Scholar]
  32. Waldum H. L., Lehy T., Brenna E., Sandvik A. K., Petersen H., Søgnen B. S., Bonfils S., Lewin M. J. Effect of the histamine-1 antagonist astemizole alone or with omeprazole on rat gastric mucosa. Scand J Gastroenterol. 1991 Jan;26(1):23–35. doi: 10.3109/00365529108996480. [DOI] [PubMed] [Google Scholar]
  33. Waldum H. L., Sandvik A. K., Brenna E., Petersen H. Gastrin-histamine sequence in the regulation of gastric acid secretion. Gut. 1991 Jun;32(6):698–701. doi: 10.1136/gut.32.6.698. [DOI] [PMC free article] [PubMed] [Google Scholar]

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