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Antisecretory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene antagonism, on gastric acid secretion in the pig

  • Allergy and Histamine
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Abstract

The antisecretory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene antagonism, on the hypersecretion of gastric acid stimulated by several secretagogues was examined in the pig. Goettingen miniature pigs with chronic gastric fistula were used. Intramuscular injection of carbachol (60 μg/kg), tetragastrin (50 μg/kg) or histamine (200 μg/kg)-induced gastric acid hypersecretion. Intraduodenal administration of DS-4574 (10 and 20 mg/kg) significantly inhibited both the hypersecretion induced by carbachol and that by tetragastrin. On the other hand, DS-4574 (50 mg/kg, intraduodenal) did not suppress histamine-induced hypersecretion. In thein vitro study, no effect on hog gastric K+-dependent ATPase activity was found at concentrations of DS-4574 from 10−7 to 10−4 M. These results were highly similar to those in the rat. The suppression of histamine release from histamine-containing cells in the gastric mucosa of the rat was concluded to be an antisecretory effect of DS-4574.

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References

  1. S. Yokohama, T. Miwa, S. Aibara, H. Fujiwara, H. Matsumoto, K. Nakayama, T. Iwamoto, M. Mori, R. Moroi, W. Tsukada and S. Isoda,Synthesis and antiallergy activity of [1,3,4] thiadiazolo[3,2,a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives. II. 6-alkyl- and 6-cycloalkylalkly derivatives. Chem. Pharm. Bull.40, 2391–2398 (1992).

    PubMed  Google Scholar 

  2. S. Aibara, M. Mori, T. Iwamoto, T. Chiba and W. Tsukada,Antagonistic action of DS-4574 against leukotriens in guineapig smooth muscle. Arch. Int. Pharmacodyn. Ther.314, 147–159 (1991).

    PubMed  Google Scholar 

  3. S. Aibara, M. Mori, M. Tsubokawa, T. Iwamoto and W. Tsukada,Antiallergic activity of 6-(2-cyclohexylethyl)-[1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one (DS-4574) in rats. Int. Arch. Allergy Immunol.98, 146–152 (1992).

    PubMed  Google Scholar 

  4. S. Aibara, M. Mori and W. Tsukada,Inhibitory effect of DS-4574 on leukotriene-or antigen-induced bronchoconstriction in guinea pigs. Int. Arch. Allergy Immunol.100, 268–273 (1993).

    PubMed  Google Scholar 

  5. S. Aibara, M. Mori, T. Iwamoto, M. Tsubokawa, H. Takamori and W. Tsukada,Effects of DS-4574, a new orally active antiallergic agent, in experimental allergic and inflammatory methods. Japan. J. Pharmacol.61, 267–276 (1993).

    Google Scholar 

  6. Y. Tabuchi and Y. Kurebayashi,Effect of DS-4574, a novel peptidoleukotriene antagonist with mast cell stabilizing action, on acute gastric lesions and gastric secretion in rats. Japan. J. Pharmacol.60, 335–340 (1992).

    Google Scholar 

  7. Y. Tabuchi, K. Kawarabayashi, T. Komada and K. Furuhama,Protective effect of DS-4574, a peptidoleukotriene antagonist with mast cell stabilizing action, on gastric mucosal injury induced by acidified ethanol in rats. Eur. J. Pharmacol.250, 197–199 (1993).

    Article  PubMed  Google Scholar 

  8. Y. Tabuchi, T. Yasuda, M. Kuno and Y. Kurebayashi,Effect of DS-4574, a novel leukotriene antagonist with mast cell stabilizating action, on gastric acid secretion in rats. Japan. J. Pharmacol.52 (suppl.), 242P (1990).

  9. N. Takeguchi, R. Joshima, M. Inoue, T. Kashiwagura and M. Morii,Effects of Cu 2+-o-phenanthroline on gastric (H ++K+)_-ATPase. Evidence for opening of a closed anion conductance by S−S cross-linking, J. Biol. Chem.258, 3094–3098 (1983).

    PubMed  Google Scholar 

  10. S. Asano, Y. Tabuchi and N. Takeguchi,Monoclonal antibody HK4001 completely inhibits K +-dependent ATP hydrolysis and H + transport of hog gastric H +,K+-ATPase, J. Biochem. (Tokyo)106, 1074–1079 (1989).

    Google Scholar 

  11. C.H. Fiske and Y. Subbarow,The colorimetric determination of phosphorus. J. Biol. Chem.66, 375–400 (1925).

    Google Scholar 

  12. J.W. Black, W. A. M. Duncan, C. J. Durant, C. R. Ganellin and M. E. Persons,Definition and antagonism of histamine H 2-receptors. Nature236, 385–390 (1972).

    PubMed  Google Scholar 

  13. D. K. Kasbekar, H. A. Ridley and J. G. Forte,Pentagastrin and acetylcholine relation to histamine in H + secretion by gastric mucosa. Am. J. Physiol.216, 961–967 (1969).

    PubMed  Google Scholar 

  14. P. K. Rangachari,Histamine release by gastric stimulants. Nature253, 53–55 (1975).

    PubMed  Google Scholar 

  15. W. Lorenz, K. Thon, H. Barth, E. Neugebauer, H.-J. Reimann and J. Kusche,Metabolism and function of gastric histamine in health and disease. J. Clin. Gastroenterol.5 (Suppl. 1), 37–56 (1983).

    Google Scholar 

  16. A. K. Sandvik, H. L. Waldum, P. M. Kleveland and B. Schulze Sognen,Gastrin produces an immediate and dose-dependent histamine release preceding acid secretion in the totally isolated, vascularly perfused rat stomach, Scand. J. Gastroenterol.22, 803–808 (1987).

    PubMed  Google Scholar 

  17. E. Bergqvist and K. J. Obrink,Gastrin-histamine as a normal sequence in gastric acid stimulation in the rabbit. Ups. J. Med. Sci.84, 145–154 (1979).

    PubMed  Google Scholar 

  18. E. Brenna and H. L. Waldum,Studies of isolated parietal and enterochromaffin-like cells from the rat. Scand.J. Gastroenterol.26, 1295–1306 (1991).

    PubMed  Google Scholar 

  19. C. Prinz, M. Kajimura, D. R. Scott, F. Mercier, H. F. Helander and G. Sachs,Histamine secretion from rat enterochromaffinlike cells, Gastroenterology105, 449–461 (1993).

    PubMed  Google Scholar 

  20. C. N. Chuang, M. Tanner, M. C. Y. Chen, S. Davison and A. H. Soll,Gastrin induction of histamine release from primary cultures of canine oxyntic mucosal cells. Am. J. Physiol.263, G460-G465 (1992).

    PubMed  Google Scholar 

  21. A. K. Nicol, M. Thomas and J. Wilson,Inhibition of gastric acid secretion by sodium cromoglycate and FPL52694. J. Pharm. Pharmacol.33, 554–556 (1981).

    PubMed  Google Scholar 

  22. R. Hakanson and G. Liedberg,The role of endogenous gastrin in the activation of gastric histidine decarboxylase in the rat. Eur. J. Pharmacol.12, 94–103 (1970).

    Article  PubMed  Google Scholar 

  23. W. Lorenz, H. Barth, J. Kusche, H. J. Reimann, A. Schmal, E. Matejka, Ch. Mathias, M. Hutzel and E. Werle,Histamine in the pig: Determination, distribution, release and pharmacological actions. Eur. J. Pharmacol.14, 155–175 (1971).

    Article  PubMed  Google Scholar 

  24. T. R. Houpt,Physiologic control of ingestive behavior in pigs. InSwine in Biomedical Research, Vol. 2 (Ed. M. E. Tumbleson) pp. 943–956, Plenum Press, New York 1986.

    Google Scholar 

  25. W. Lorenz, St. Halbach, M. Gerant and E. Werle,Specific histidine decarboxylases in the gastric mucosa of man and other mammals. Biochem. Pharmacol.18, 2625–2637 (1969).

    Article  PubMed  Google Scholar 

  26. R. Hakanson and F. Sundler,Histamine-producing cells in the stomach and their role in the regulation of acid secretion. Scand. J. Gastroenterol.26, suppl. 180, 88–94 (1991).

    Google Scholar 

  27. S. Mardh, Y.-H. Song, C. Carlsson and T. Bjorkman,Mechanisms of stimulation of acid production in parietal cells isolated from the pig gastric mucosa. Acta. Physiol. Scand.131, 589–598 (1987).

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 183, Tokyo, Japan

    Y. Yamashika & E. Kokue

  2. Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., 16-13, Kita-Kasai 1-chome, Edogawa-ku, 134, Tokyo, Japan

    Y. Tabuchi

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  1. Y. Yamashika
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Yamashika, Y., Tabuchi, Y. & Kokue, E. Antisecretory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene antagonism, on gastric acid secretion in the pig. Agents and Actions 41, 17–20 (1994). https://doi.org/10.1007/BF01986387

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  • DOI: https://doi.org/10.1007/BF01986387

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