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Augmentation of pentagastrin stimulated gastric secretion in the heidenhain pouch dog by amodiaquine: Inhibition of histamine methyltransferase in vivo?

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Abstract

In 9 dogs, whose maximum gastric acid response to pentagastrin was evoked by 6 μg/kg, the total gastric secretion as well as the peak gastric secretion was enhanced by amodiaquine. The optimum dose of this antimalarial drug was 2 mg/kg, whereas 0.25 mg/kg were without effect and 3 mg/kg reduced already the augmentation of gastric secretion by this substance. The increase in acid output by amodiaquine was greater than that in volume. The total secretion was more enhanced than the peak secretion, which means a longer duration of the amodiaquine potentiated gastric secretion elicited by pentagastrin, than that without application of amodiaquine contrary to that stimulated by exogenous histamine.

Amodiaquine itself did not stimulate gastric acid secretion, in contrast to prostigmine and carbachol. Thus amodiaquine seemed not to enhance gastric secretion by a direct or indirect parasympathomimetic action. The question whether amodiaquine acted on gastric secretion in a specific way and not by parasympathomimetic effects, led to investigations in several exocrine glands. In salivary glands, amodiaquine did neither stimulate the secretion in all doses investigated nor did it enhance the pilocarpine and acetylcholine induced salivation with any significance and regularity. Also the pancreatic and biliary secretion was neither stimulated by amodiaquine nor was the secretin induced secretion of the pancreas and liver augmented by amodiaquine. Thus the enhancing effect of this drug on the histamine and pentagastrin stimulated gastric secretion was very likely specific for the gastric mucosa and not due to a parasympathomimetic action of the drug.

In contrast to the findings in various exocrine glands of the gastrointestinal tract, the arterial hypotension following the i.v. injection of acetylcholine was increased specifically by a preceeding i.v. injection of amodiaquine, whereas the equi-effective actions of histamine, serotonin and bradykinin as well as the hypertension by epinephrine and norepinephrine were not influenced by amodiaquine. This specific effect of the antimalarial drug very probably was not caused by an inhibition of the unspecific choline esterase in the blood.

Since in exocrine glands no evidence could be found for a parasympathomimetic action or other modes of action of amodiaquine, it seemed probable that amodiaquine potentiated the histamine and pentagastrin stimulated gastric secretion by an inhibition of histamine methyltransferase in vivo.

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References

  1. W. Lorenz, E. Matejka, A. Schmal, W. Seidel, H. J. Reimann, R. Uhlig andG. Mann,A Phylogenetic Study on the Occurrence and Distribution of Histamine in the Gastro-Intestinal Tract and other Tissues of Man and Various Animals. Comp. General Pharmac. (1973, in press).

  2. W. Lorenz andK. Pfleger,Stoffwechsel und physiologische Funktion von Histamin im Magen, Klin. Wschr.46, 57 (1968).

    Google Scholar 

  3. R. Håkanson,New Aspects of the Formation and Function of Histamine, 5-Hydroxytryptamine and Dopamine in Gastric Mucosa, Acta physiol. scand. suppl.340, 1 (1970).

    Google Scholar 

  4. N. G. Waton,Histamine and the Parietal Cell, Am. J. Digest. Dis.16, 921 (1971).

    PubMed  Google Scholar 

  5. D. D. Brown, R. Tomchick andJ. Axelrod,The Distribution and Properties of a Histamine-Methylating Enzyme, J. Biol. Chem.234, 2948 (1959).

    PubMed  Google Scholar 

  6. K. S. Kim, B. Backus, H. Harris andP. Rourke,Distribution of Diamine Oxidase and Imidazole-N-Methyltransferase along the Gastro-Intestinal Tract, Comp. Biochem. Physiol.31, 137 (1969).

    PubMed  Google Scholar 

  7. B. O. Amure andM. Ginsburg,Effects of Chlorpromazine and Bromolysergic Acid Diethylamide on Gastric Secretion of Acid Induced by Histamine in Rats, Br. J. Pharmac.22, 520 (1964).

    Google Scholar 

  8. B. O. Amure andM. Ginsburg,Inhibitors of Histamine Catabolism and the Action of Gastrin, Br. J. Pharmac.23, 476 (1964).

    Google Scholar 

  9. W. Lorenz, H. Barth andE. Werle,Histamine and Histamine Methyltransferase in the Gastric Mucosa of Man, Pig, Dog and Cow, Naunyn-Schmiedebergs Arch. Pharmak.267, 421 (1970).

    Google Scholar 

  10. J. Kusche, W. Lorenz, H. Hahn andE. Werle,Occurrence and Properties of Diamine Oxidases in Salivary Glands and Gastric Mucosa of Man and other Mammals, Naunyn-Schmiedebergs Arch. Pharmak.,264, 265 (1969).

    Google Scholar 

  11. T. M. Lin, A. C. Ivy, E. Karvinen andE. K. Ivy,Effect of a Histaminase Inhibitor (Aminoguanidine) on the Gastric Secretory Response to Exogenous Histamine, Am. J. Physiol.186, 231 (1956).

    PubMed  Google Scholar 

  12. H. Barth, W. Lorenz, K. Goecke, K. Herrmann, W. Seidel andH. Troidl, Histamine Methyltransferase in Man, Dog and Pig: Distribution, Purification and Properties Naunyn-Schmiedebergs Arch. Pharmak.274, Suppl. R 14 (1972a).

  13. H. Barth, H. Troidl, K. Goecke, K. Herrmann, W. Seidel andW. Lorenz,Histamine Methyltransferase: Distribution, Purification and Inhibition in vitro and in vivo, J. Pharmac. (Paris)3, 521 (1972b).

    Google Scholar 

  14. H. Troidl, H. Barth, W. Lorenz, H. Rohde andK. Goecke,Effect of Amodiaquine on Gastric Histamine Methyltransferase and on Histamine Stimulated Gastric Secretion, Br. J. Pharmac. (1973, in press).

  15. W. Lorenz, H. Troidl, G. Feifel, A. Huhnd, H. Barth andH. Rohde,Inhibition of Gastric Histamine Methyltransferase by Amodiaquine in vitro and in vivo, Acta Pharmac. Toxicol.29, Suppl. 4, 31 (1971).

    Google Scholar 

  16. V. H. Cohn,Inhibition of Histamine Metabolism (Methylation) by Antimalarial Drugs, Fed. Proc.23, 691 (1966).

    Google Scholar 

  17. K. S. Kim andV. H. Cohn,Inhibition of Histamine Metabolism, Pharmacologist8, 185 (1966).

    Google Scholar 

  18. H. Troidl, W. Lorenz, H. Barth, W. Seidel, H. Rohde, K. Goecke, A. Schmal andH. Hamelmann,Studies on a Mechanism of Enhancement of Maximum Gastric Secretory Response: Its Possible Importance in Recurrent Ulcers after Surgical Treatment, Res. Exp. Med.157, 201 (1972).

    Google Scholar 

  19. S. Emås, K. G. Svan andE. D. Jacobson,Methods of Studying Gastric Secretion, in:Handbook of Physiology, sect. 6, vol. II (Williams & Wilkins Comp. Baltimore 1967), p. 743.

    Google Scholar 

  20. R. V. De Vito andH. N. Harkins,Techniques in Heidenhein Pouch Experiments, J. appl. Physiol.14, 138 (1958).

    Google Scholar 

  21. E. Werle andW. Lorenz,Specheldrüsensekretion nach Pilocarpin, Histamin und Kininen, Arch. int. Pharmacodyn.161, 477 (1966).

    PubMed  Google Scholar 

  22. W. Lorenz, G. Haubensak, M. Hutzel andE. Werle,Histaminliberierung in Gl. submaxillaris und Pankreas durch Parasympathicomimetica, Peptidhormone, Histamin und Mepyramin, Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.260, 416 (1968).

    Google Scholar 

  23. G. W. Snedecor andW. G. Cochran,Statistical Methods (Iowa State University Press, Ames, Iowa 1968).

    Google Scholar 

  24. S. Andersson andM. I. Grossman,Effect of Vagal Denervation of Pouches on Gastric Secretion in Dogs with Intact or Resected Antrum, Gastroenterology48, 449 (1965).

    PubMed  Google Scholar 

  25. F. Erjavec, M. A. Beaven andB. B. Brodie,Uptake and Release of 3 H-Histamine in Cat Submaxillary Gland, Fed. Proc.26, 237 (1967).

    PubMed  Google Scholar 

  26. W. Lorenz, H. Barth, G. Feifel andE. Werle,Histamine Methyltransferases in Salivary Glands and Gastric Mucosa of Man, Dog, Pig and Cow, Naunyn-Schmiedebergs Arch. Pharmak.266, 395 (1970).

    Google Scholar 

  27. H. Gastpar andW. Lorenz,Histaminstoffwechsel in der Glandula submandibularis und in der Glandula parotis des Menschen und verschiedener Säugetiere, Arch. klin. exp. Ohr.-Nas.-Kehlkopfheilk.198, 293 (1971).

    Google Scholar 

  28. W. Lorenz, A. Reimann-Huhnd, J. Kusche, H. Barth, G. Haubensak, M. Hutzel, A. Schmal, M. Gerant, A. Wächter, E. Matejka, H. Hahn andE. Werle,Histamine and Salivary Secretion, Satellite Symp. XXII. Intern. Congress in Physiology, 1–8 August 1971, Lodz, Poland (in press).

  29. W. Lorenz, D. Maroske, A. Reimann-Huhnd, H. Sihlbom andP. Keck,Histamine, Methylated Histamines and Parasympathomimetic Stimulation of Salivary Secretion, Naunyn-Schmiedebergs Arch. Pharmak.277, R44 (1973).

    Google Scholar 

  30. B. Fjalland andV. Pedersen,On the Role of Biogenic Amines in the control of Gastric Secretion in Rats, Acta Pharmac. Toxicol.29, Suppl. 4, 13 (1971).

    Google Scholar 

  31. W. M. Sams,Chloroquine: Mechanism of Action, Mayo Clin. Proc.42, 300 (1967).

    PubMed  Google Scholar 

  32. V. H. Cohn,Inhibition of Histamine Methylation by Antimalarial drugs, Biochem. Pharmac.14, 1686 (1965).

    Google Scholar 

  33. W. Lorenz, A. Schauer, St. Heitland, R. Calvoer andE. Werle,Biochemical and Histochemical Studies on the Distribution of Histamine in the Digestive Tract of Man, Dog and other Mammals, Naunyn-Schmiedebergs Arch. Pharmak.265, 81 (1969).

    Google Scholar 

  34. D. Aures, R. Håkanson, Ch. Owman andB. Sporrong,Cellular Stores of Histamine and Monoamines in the Dog Stomach, Life Sci.7, 1147 (1968).

    Google Scholar 

  35. R. Håkanson, Ch. Owman, N.-O. Sjöberg andB. Sporrong,Amine Mechanisms in Enterochrom-Affin and Enterochrom-Affin Like Cells of Gastric Mucosa in Various Mammals, Histochemie21, 189 (1970).

    PubMed  Google Scholar 

  36. W. Lorenz, A. Schauer, St. Heitland, E. Matejka andE. Werle,Biochemical and Histochemical Studies on Histamine in the Digestive Tract: Distribution in Different Chordates and Cellular Stores in the Dog, Nanyn-Schmiedebergs Arch. Pharmak.264, 274 (1969).

    Google Scholar 

  37. W. Lorenz, A. Doenicke, G. Feifel, K. Messmer, R. Meier, L. Bennesch, H. Barth, J. Kusche, M. Hutzel andE. Werle,Histamine Release in Man by Propanidid (Epontol ®),Gelatin (Haemaccel ®),Histalog, Pentagastrin and Insulin, Naunyn-Schmiedebergs Arch. Pharmak.266, 396 (1970).

    Google Scholar 

  38. L. R. Johnson, R. S. Jones, D. Aures andR. Håkanson,Effect of Antrectomy on Gastric Histidine Decarboxylase Activity in the Rat, Am. J. Physiol.216, 1051 (1969).

    PubMed  Google Scholar 

  39. J. A. Roth andA. C. Ivy,The Synergistic Effect of Caffeine upon Histamine in Relation to Gastric Secretion, Am. J. Physiol.107, 400 (1944).

    Google Scholar 

  40. R. A. Payne andA. W. Kay,The Effect of Vagotomy on the Maximal Acid Secretory Response to Histamine in Man, Clin. Sci.22, 373 (1961).

    Google Scholar 

  41. E. P. Passaro, I. E. Gillespie andM. I. Grossman,Potentiation between Gastrin and Histamine in Stimulation of Gastric Secretion, Proc. Soc. Exp. biol. Med.114, 50 (1963).

    PubMed  Google Scholar 

  42. I. E. Gillespie andM. I. Grossman,Potentiation between Urecholine and Gastrin Extract and between Urecholine and Histamine in the Stimulations of Heidenhain Pouches, Gut5, 71 (1964).

    Google Scholar 

  43. M. M. Cohen, T. Holubitzky andD. B. Harrison,Caffeine and Pentagastrin Stimulation of Human Gastric Secretion, Gastroenterology61, 440 (1971).

    PubMed  Google Scholar 

  44. L. Olbe,Potentiation of Acid Sham Feeding Responses in Pavlov Dogs by Histamine and by Mesenteric-Caval Vein Anastomosis, Acta Physiol. scand.66, 473 (1966).

    PubMed  Google Scholar 

  45. S.J. Konturek andJ. Olesky,Potentiation between Pentapeptide (ICI 50123) and Histamine in the Stimulation of Gastric Secretion in Man, Gastroenterology53, 912 (1967).

    PubMed  Google Scholar 

  46. R. G. Checketts, I. E. Gillespie andA. W. Kay,Insulin Potentiation of the Augmented Histamine Response, Gut9, 863 (1968).

    Google Scholar 

  47. L. R. Johnson andM. I. Grossman,Potentiation of Gastric Acid Response in the Dog, Gastroenterology56, 687 (1969).

    Google Scholar 

  48. A. R. Cooke,Potentiation of Acid Secretion in Dogs Am. J. Physiol.216, 969 (1969).

    Google Scholar 

  49. A. M. Brooks andM. I. Grossman,Maximal Acid Responses of Pavlov Pouches to Food and Histamine Gut11, 153 (1970).

    PubMed  Google Scholar 

  50. A. R. Cooke,Potentiation of Acid Output in Man by a Distention Stimulus, Gastroenterology58, 633 (1970).

    PubMed  Google Scholar 

  51. V. Varro, J. Kiss andM. Mignon,Potentiation of Gastric Acid Response to Increasing Doses of Pentagastrin by Subthreshold Doses of Metacholine in Heidenhain Pouch Dogs, Biol. Gastro-Enterol.II, 169 (1971).

    Google Scholar 

  52. A. Dinbar andM. I. Grossman,Interaction of Stimulations of Acid Secretion in Cat, Gastroenterology62, 242 (1972).

    PubMed  Google Scholar 

  53. J. R. N. Curt, J. Isaza, E. R. Woodward andL. R. Dragstedt,Potentiation between Intestinal and Gastric Phases of Acid Secretion in Heidenhain Pouches, Arch. Surg.103, 709 (1971).

    PubMed  Google Scholar 

  54. P. H. Jordan,Relationship between Stimulating Mechanisms of Gastric Secretion in Dogs, JAMA199, 399 (1967).

    PubMed  Google Scholar 

  55. R. A. Gregory,Gastric Secretory Responses after Portal Venous Ligation, J. Physiol. (London)144 123 (1958).

    Google Scholar 

  56. M. I. Grossman,Stimulation of Secretion of Acid by Distention of Denervated Fundic Pouches in Dogs, Gastroenterology41, 385 (1961).

    PubMed  Google Scholar 

  57. R. B. Quintana, C. de la Rose andL. R. Dragstedt,The Effect of Endogenous Gastrin on Histamine-Induced Gastric Secretion, Am. J. Digest. Dis.10, 745 (1965).

    PubMed  Google Scholar 

  58. L. S. Goodman andA. Gilman,The Pharmacological Basis of Therapeutics, 4th ed. (The Mac Millan Company, London-Toronto 1971), p. 24.

    Google Scholar 

  59. M. I. Grossman,Potentiation, a Reply, Gastroenterology55, 815 (1969).

    Google Scholar 

  60. G. M. Makhlouf andA. L. Blum,Kinetics of the Taste Response to Chemical Stimulation: a Theory of Acid Taste in Man, Gastroenterology63, 67 (1972).

    PubMed  Google Scholar 

  61. J. H. Gaddum,Pharmacology (Oxford University Press, London, New York, Toronto 1959), p. 504.

    Google Scholar 

  62. G. M. Makhlouf, J. P. A. Mac Manus andJ. R. Knill,Quantitative Aspects of Synergism and Inhibition of Gastric Acid Secretion, Gastroenterology54, 532 (1968).

    PubMed  Google Scholar 

  63. A. M. Brooks, L. R. Johnson andM. I. Grossman,Effect of Combinations of Histamine and Pentagastrin on Gastric Secretion in Man and Dog, Gastroenterology58, 470 (1970).

    Google Scholar 

  64. M. Garcia, C. Miyares andF. Sainz An Eserine-Like Action of Chloroquine, Can. J. Physiol. Pharmac.49, 492 (1971).

    Google Scholar 

  65. J. C. Schwartz andJ. M. Andre,Studies on the Inhibition of Histamine (HA) Methylation in Mice, Agents and Actions (this issue, in press).

  66. H. Barth, W. Lorenz andI. Niemeyer,Inhibition and Activation of Histamine Methyltransferase by Methylated Histamines, Hoppe-Seylers Z. physiol. Chem. (1973, in press).

  67. M. A. Reilly andR. W. Schayer,In vivo Studies on Histamine Metabolism and its Inhibition, Br. J. Pharmac.38, 478 (1970).

    Google Scholar 

  68. F. Erjavec, M. A. Beaven andB.-B. Brodie,Role of Histamine and Methylhistamine in Salivation, Pharmacologist7, 153 (1965).

    Google Scholar 

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Authors and Affiliations

  1. Division of Experimental Surgery and Pathological Biochemistry at the Surgery Clinic of the University, Marburg an der Lahn, Germany

    H. Troidl, W. Lorenz, H. Barth, H. Rohde, G. Feifel, A. Schmal, K. Goecke, A. Reimann-Huhnd & W. Seidel

  2. Surgical Clinic of University, Munich, Germany

    H. Troidl, W. Lorenz, H. Barth, H. Rohde, G. Feifel, A. Schmal, K. Goecke, A. Reimann-Huhnd & W. Seidel

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  1. H. Troidl
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Supported by grants from Deutsche Forschungsgemeinschaft (Lo 199/3) and E. Merck AG, Darmstadt.

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Troidl, H., Lorenz, W., Barth, H. et al. Augmentation of pentagastrin stimulated gastric secretion in the heidenhain pouch dog by amodiaquine: Inhibition of histamine methyltransferase in vivo?. Agents and Actions 3, 157–167 (1973). https://doi.org/10.1007/BF01965726

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