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Stoffwechsel und physiologische Funktion von Histamin im Magen

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Zusammenfassung

1. Histamin kommt in der Magenwand aller untersuchten Arten in hoher Konzentration vor, in der Schleimhaut vor allem in oder nahe bei Belegzellen, mucoiden Drüsenzellen, Mastzellen und enterochromaffinen Zellen.

2. Histamin wird in der Magenschleimhaut aller untersuchten Arten in ausreichendem Maße vor allem durch die spezifische Histidindecarboxylase gebildet, die sich in erster Linie in oder in der Nähe von den Belegzellen und mucoiden Drüsenzellen befindet. Die unspezifische HDC kommt in der Mucosa vor allem in den enterochromaffinen Zellen vor.

3. Die Histamininaktivierung im Magengewebe erfolgt bei Mensch, Katze, Kaninchen, Meerschweinchen und Maus überwiegend durch Histaminmethyltransferase, bei der Ratte durch Diaminoxydase.

4. Histamin stimuliert die Magensaftsekretion bei allen untersuchten Arten. Zwischen Histamingehalt der Schleimhaut, Histaminbildung und Empfindlichkeit der Belegzellen gegenüber Histamin besteht eine Korrelation.

5. Histamin wird durch eine große Zahl von Substanzen aus Mastzell- und Nichtmastzellspeichern freigesetzt. Beweisgründe werden erbracht, daß Gastrin und cholinerge Mechanismen die Magensaftsekretion durch Freisetzung von Histamin stimulieren. Histamin ist danach der finale Chemostimulator.

6. Durch Verdauungsvorgänge, Gastrin und Anlegen eines portocavalen shunts kommt es zu vermehrter Histaminbildung durch Induktion der spez. HDC, ebenso durch Glucocorticoide, Thyroxin und entzündungshemmende Substanzen wie Indomethazin, Salicylate, Phenylbutazon, Fluphenaminsäure. Auch Streß, Kältereiz und Serotonin haben diese Wirkung.

7. Die Wirkung der Antihistaminica auf die Magensaftsekretion ist noch nicht befriedigend geklärt. Die Hemmung der Magensaftsekretion bei der Ratte durch das Antihistaminicum Phloxin ist sicher spezifisch.

8. Bei der Ratte ist die physiologische Wirkung von Histamin als finalem Chemostimulator der Magensekretion erwiesen, bei allen anderen Species wahrscheinlich.

Summary

1. The stomach of men and all of the animals, which have been investigated, contains histamine in a high concentration. In the mucosa histamine is found especially in or near the parietal cells (fundus and corpus), by the mucoid cells (cardia and pyloric glands, mucous neck cells), but also in the mast cells and enterochromaffine cells. In the submucosa and muscularis propria histamine could be demonstrated in mast cells, muscle fibers of the smooth muscle and arterioles by autoradiography and fluorescence microscopy. Further its localisation is suggested in the wall of capillaries and in nerves. So a great number of cellular pools for histamine in the gastric wall must be postulated. It is possible that histamine changes its position between these pools.

2. In the stomach of men and all of the animals which have been investigated, histamine is formed in a sufficient amount by the specific histidine decarboxylase. These results have been obtained by isotopic and nonisotopic assays. The highest activity of the specific HDC mostly is demonstrated in the fundus, the lowest in the pylorus. The enzyme is found in or near by parietal cells and mucoid cells, its localisation in mast cells and endothel cells is suggested. The activity of the unspecific HDC is fairly the same in all regions of gastric mucosa. The enzyme is found in the enterochromaffine cells, but is suggested to be in mast cells and nerves, too.

3. In man, cat, rabbit, guinea pig and mice histamine in the gastric tissue is inactivated especially by histamine methyltransferase, by diamine oxidase especially in the rat. The formation of histamine nucleotide, acetylation and transamination may be important too.

4. Histamine stimulates the gastric secretion in men and all of the animals which have been investigated, with exception of lower amphibians and elasmobranch fishes which possibly have got a dose of histamine, which has not been sufficient for stimulation. Histamine in every way of application stimulates the gastric secretion, but applicated orally, high amounts (50–100 mg) are needed. A correlation exists between the histamine content, the formation of histamine and the sensitivity of the parietal cells with respect to histamine stimulation. The gastric juice after histamine stimulation shows a high acidity and a great volumen of juice, but the pepsin and mucin content is low in many species.

5. From mast cells compound 48/80, d-tubocurarine and antihistaminics liberate histamine, from nonmast cell storages, especially in the gastric mucosa, gastrin and parasympathicomimetic mechanisms stimulate gastric secretion by liberation of histamine. Histamine is the final chemostimulator. The importance of liberation and formation of histamine in striatic muscles during chronically elevated muscle tonus for development of high basis secretion and duodenal ulcer is discussed.

6. During digestion, by gastrin injection and portocaval shunt histamine formation is elevated by induction of the specific HDC. Hormonal influences like injection of glucocorticoids, thyroxine, and antiinflammatory drugs, for instance indomethazine, salicylic acid, phenylbutazone and fluphenamic acid stimulate histamine formation in the same way, also stress by restraint and cold or serotonin. Glucocorticoids inhibit the histamine formation in all organs and tissues except the stomach.

7. The investigation of the action of antihistaminics on gastric secretion today has not still obtained satisfactoring results. Parenterally applicated the antihistaminics have been found to be ineffective in all species except the pigeon. By local or i.a. application immediately before the stomach they inhibit the gastric secretion. In the dog, parenterally applicated they are effective, if tween 20 simultaneously is injected. The question of specific or unspecific action of antihistaminics (by mucosal injury or by cholinolytic action) appears to be not completely cleared, especially because in salivary glands of dogs it has been shown that antihistaminics injected immediately before the gland inhibit the secretion of saliva in a specific way. Phloxine inhibits the gastric secretion in the rat specifically.

8. In the rat complete evidence is presentated, that histamine is the physiological final chemostimulator of the gastric secretion. In men and all of the other investigated animals evidence is strongly supported, but not completed, that histamine acts on the gastric tissue in the same way. The pecularities of the rat with respect to the metabolism of histamine and gastric secretion should not be exaggerated.

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    Wilfried Lorenz & Klaus Pfleger

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Unserem verehrten Lehrer, Herrn Prof. Dr. Dr.E. Werle, zum 65. Geburtstag in Dankbarkeit gewidmet.

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Lorenz, W., Pfleger, K. Stoffwechsel und physiologische Funktion von Histamin im Magen. Klin Wochenschr 46, 57–71 (1968). https://doi.org/10.1007/BF01747470

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