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The role of gastric histamine release in the acid secretory response to pentagastrin and methacholine in the dog

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Abstract

We have previously demonstrated that both pentagastrin and methacholine can stimulate histamine release from the canine stomach during short term administration of the secretagogues into the gastrosplenic artery. In this study we tested the hypothesis that gastric histamine release determines the acid secretory response to acid secretagogues. Increasing doses of pentagastrin (2, 6, and 20 ng/kg/min) and methacholine (0.1, 0.3, and 1µg/min) were infused into the gastro-splenic artery in dogs, while gastric acid output, histamine and Nτ-methyl histamine secretory rates were monitored. Histamine and Nτ-methyl histamine concentrations in plasma were measured using GC/NICI-MS. Increasing doses of pentagastrin resulted in increasing gastric output. Total histamine secretory rate expressed as the sum of histamine and Nτ-methyl histamine secretory rate showed a significant increase above basal with the two highest doses of pentagastrin. Regression analysis correlating the dose of pentagastrin to gastric acid output gave a correlation coefficient of 0.586 which was very significant. Regression analysis correlating the total histamine secretory rate to acid output gave a correlation coefficient of 0.498 which was also very significant. Increasing doses of methacholine also resulted in a dose-dependent increase in acid output. Histamine secretory rates showed a statistically significant increase above basal only at the 1µg/min infusion rate, however, the total histamine secretory rates (histamine + Nτ-methyl histamine) were no longer significant at any of the doses of methacholine. Regression analysis correlating the dose of methacholine to gastric acid output gave a correlation coefficient of 0.571 which was significant, while correlating the histamine secretory rate to acid output gave a correlation coefficient of 0.338, not significant, which decreased to 0.079 when the total histamine secretory rates were correlated to acid output. Sixty-eight min infusions of pentagastrin demonstrated a dose-dependent, pulse-like but persistent increase in histamine secretory rate above basal, while long-term infusion of methacholine gave a flat, low-grade histamine stimulation. These data suggest that for pentagastrin, both the dose of pentagastrin and the amount of histamine released determine the acid secretory response with this secretagogue, but the dose of pentagastrin correlates more strongly with acid output. During cholinergic stimulated acid output, only the dose of methacholine correlates with acid output. Thus, for cholinergic stimulated gastric acid output, histamine is not likely to be a final mediator, but for gastrin both its direct action at the parietal cell and the amount of histamine released appear to contribute to the acid secretory response.

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References

  1. Grossman MI, Konturek SJ. Inhibition of acid secretion in dog by metiamide, a histamine antagonist acting on H2 receptors. Gastroenterol 1974;66:517–21.

    Google Scholar 

  2. Burland WL, Duncan WAM, Hesselbo T, Mills JG, Sharpe PC, Haggie SJ et al. Pharmacological evaluation of cimetidine, a new histamine H2-receptor antagonist, in healthy man. Br J Clin Pharmacol 1975;2:481–6.

    Google Scholar 

  3. Code CF. Histamine and gastric secretion: A later look 1955–1965. Fed Proc 1965;24:1311–21.

    Google Scholar 

  4. Black JW, Shankley NP. How does gastrin act to stimulate oxyntic cell secretion. Trends Pharmacol Sci 1987;8:486–90.

    Google Scholar 

  5. Kabekar DK, Ridley HA, Forte J.G. Pentagastrin and acetylcholine relation to histamine in H+ secretion by gastric mucosa. Am J Physiol 1969;216:961–7.

    Google Scholar 

  6. Main IHM, Pearce JB. Increased histamine output from the isolated gastric mucosa of the rat in response to pentagastrin and methacholine. Br J Pharmacol 1982;76:51–9.

    Google Scholar 

  7. Ekblad EBM. Histamine: the sole mediator of pentagastrin-stimulated acid secretion. Acta Physiol Scand 1985;125:135–43.

    Google Scholar 

  8. Sandvik AK, Waldum HL, Kleveland PM, 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;22:803–8.

    Google Scholar 

  9. Johnson LR, Grossman MI. Potentiation of gastric acid response in the dog. Gastroenterol 1969;56:687–92.

    Google Scholar 

  10. Soll AH. The interaction of histamine with gastrin and carbamylcholine on oxygen uptake by isolated mammalian parietal cells. J Clin Invest 1978;61:381–9.

    Google Scholar 

  11. Soll AH, Amirian DA, Thomas LP, Reedy TJ, Elashoff JD. Gastrin receptors on isolated canine parietal cells. J Clin Invest 1984;73:1434–47.

    Google Scholar 

  12. Lorenz W, Schauer A, Heitland St, Calvoer R, Werle E. Biochemical and histochemical studies on the distribution of histamine in the digestive tract of man, dog and other mammals. Naunyn-Schmiedebergs Arch Pharmak 1969;265:81–100.

    Google Scholar 

  13. Aures D, Hakanson R, Owman CH. Cellular stores of histamine and monoamines in the dog stomach. Life Sci 1968;7:1147–53.

    Google Scholar 

  14. Soll AH, Toomey M, Culp D, Shanahan F, Beaven MA. Modulation of histamine release from canine fundic mucosal mast cells. Am J Physiol 1988;254:G40–8.

    Google Scholar 

  15. Gerber JG, Payne NA. The role of gastric secretagogues in regulating gastric histamine release in vivo. Gastroenterol 1992;102:403–8.

    Google Scholar 

  16. Chuang GN, Tanner M, Chen MCY, Davidson S, Soll AH. Gastrin induction of histamine release from primary cultures of canine oxyntic mucosal cells. Am J Physiol 1992;263:G460–5.

    Google Scholar 

  17. Wilcoxon F, Wilcox RA. editors. Some rapid approximate statistical procedures. Pearl River, New York; Lederle Laboratories, 1964:11–2.

    Google Scholar 

  18. Code CF, Green WER, Kennedy JC, Ritchie HD, Schlegel JF. Metabolism of histamine in secreting intact and isolated canine stomach. Am J Physiol 1976;230:219–27.

    Google Scholar 

  19. Albinus M, Sewing K-F. Histamine uptake and metabolism in intact isolated parietal cells. Agents Actions 1981;11:223–7.

    Google Scholar 

  20. Wollin A. Histamine uptake and its methylation by isolated oxyntic cells. Clin Invest Med 1987;10:136–9.

    Google Scholar 

  21. Håkanson R, Böttcher G, Ekblád E, Panula AH, Simonsson M, Dohlsten M et al. Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies. Histochem 1986;86:5–17.

    Google Scholar 

  22. Sandvik AK, Kleveland PM, Waldum HL. Muscarinic M2 stimulation releases histamine in the totally isolated, vascularly perfused rat stomach. Scand J Gastroenterol 1988;23:1049–56.

    Google Scholar 

  23. Dimaline R, Sandvik AK. Histamine decarboxylase gene expression in rat fundus is regulated by gastrin. FEBS Lett 1991;281:20–2.

    Google Scholar 

  24. Schmidtler J, Schepp W, Schusdziarra V, Classen M. Effect of amino acids on H+ production by isolated rat parietal cells. Digestion 1989;44:211–6.

    Google Scholar 

  25. Soll AH. Potentiating interactions of gastric stimulants on [14C]-aminopyrine accumulation by isolated canine parietal cells. Gastroenterol 1982;83:216–23.

    Google Scholar 

  26. Lorenz W, Troidl H, Barth H, Rohde H, Schulz S, Becker H et al. Stimulus-secretion coupling in the human and canine stomach: Role of histamine. In: Case RM, Goebell H, editors. Stimulus Secretion Coupling in the Gastrointestinal Tract. Lancester: MTP Press, 1976:171–90.

    Google Scholar 

  27. Mardh S, Norberg L, Ljungström M, Wollert S, Nyrén O, Gustavsson S. A method for in vitro studies on acid formation in human parietal cells. Stimulation by histamine, pentagastrin and carbachol. Acta Physiol Scand 1985;123:349–54.

    Google Scholar 

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

    Google Scholar 

  29. Man WK, Li SK, Mathie RT, Spencer J. Effect of gastric stimulants on histamine release and circulatory responses. Agents Actions, 1992;C365–7.

  30. Soll AH. Secretagogue stimulation of [14C] aminopyrine accumulation by isolated canine parietal cells. Am J Physiol 1980;238:G366–75.

    Google Scholar 

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Supported in part by Public Health Service grant NIH R01 DK38504.

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Gerber, J.G., Payne, N.A. The role of gastric histamine release in the acid secretory response to pentagastrin and methacholine in the dog. Inflamm Res 44, 327–334 (1995). https://doi.org/10.1007/BF01796263

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  • DOI: https://doi.org/10.1007/BF01796263

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