The Role of Adenosine on the Gastric Acid Secretory Response

  • J. G. Gerber
  • N. A. Payne
Conference paper


Theophylline, an alkylxanthine, has been in extensive clinical use for the treatment of bronchospastic lung disease because the drug causes bronchial smooth muscle relaxation. One side effect associated with its use is dyspepsia, and the drug has been found to stimulate gastric acid production in man (Krasnow et al., 1949; Foster et al., 1979). The mechanism by which theophylline increases gastric acid output has been presumed to be secondary to parietal cell phosphodiesterase inhibition. Biochemically, this hypothesis has a solid basis because histamine stimulates parietal cell acid production by activating adenylate cyclase, resulting in the elevation of cellular cyclic AMP (Wollin et al., 1979). Thus, a phosphodiesterase inhibitor would be expected to enhance the cellular cAMP concentration to histamine stimulation. However, the concentration of theophylline that results in phosphodiesterase inhibition in various tissues is consistently above 50μM (Butcher et al., 1962; Smellie et al., 1979). The therapeutic plasma concentration of theophylline in man is 50 to 100μM. Thus, it seemed unlikely that the mechanism of enhanced acid secretion to theophylline is secondary to phosphodiesterase inhibition. Since many of the alkylxanthines are also competitive antagonists of the cell surface adenosine receptors, we explored the hypothesis that adenosine is a direct inhibitor of gastric acid output. We chose to explore this hypothesis in the dog model because of the capacity to examine the effect of adenosine both in the in vivo gastric fistula dog and in the in vitro isolated gastric cell preparation. In addition, the gastric physiology and anatomy of the dog resembles the human.


Acid Secretion Adenosine Receptor Parietal Cell Gastric Acid Secretion Gastric Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Butcher, R.W. and Sutherland, E.W., 1962, Adenosine 3’,5’-phosphate in biological materials. I. Purification and properties of cyclic 3’,5’-nucleotide phosphodiesterases and use of this enzyme to characterize 3’,5’-phosphate in human urine, J. Biol. Chem. 237:1244–1250.PubMedGoogle Scholar
  2. Foster, L.J., Trudeau, W.L. and Goldman, A.L, 1979, Bronchodilator effects on gastric acid secretion, JAMA 241:2613–2615.PubMedCrossRefGoogle Scholar
  3. Gerber, J.G., Fadul, S., Payne, N.A. and Nies, A.S., 1984, Adenosine: A modulator of gastric acid secretion in vivo, J. Pharmacol. Exp. Ther. 231:109–113.PubMedGoogle Scholar
  4. Gerber, J.G., Nies, A.S. and Payne, N.A., 1985a, Adenosine receptors on canine parietal cells modulate gastric acid secretion to histamine, J. Pharmacol. Exp. Ther. 233:623–627.PubMedGoogle Scholar
  5. Gerber, J.G., Payne, N.A., Fadul, S. and Nies, A.S., 1985b, Cholinergic mechanism of acid secretion in the dog: An in vivo and in vitro comparison, Eur. J. Pharmacol. 106:373–380.CrossRefGoogle Scholar
  6. Gerber, J.G. and Payne, N.A., 1988, Endogenous adenosine modulates gastric acid secretion to histamine in canine parietal cells, J. Pharmacol. Exp. Ther. 244:190–194.PubMedGoogle Scholar
  7. Krasnow, S. and Grossman, M.I., 1949, Stimulation of gastric secretion in man by theophylline ethylenediamine, Proc. Soc. Exp. Biol. Med. 71:335–336.PubMedGoogle Scholar
  8. Meghji, P., Holmquist, C.A. and Newby, A.C., 1985, Adenosine formation and release from neonatal rat heart cells in culture, Biochem. j. 229:799–805.PubMedGoogle Scholar
  9. Osswald, H., Nabakowski, G. and Hermes, H., 1980, Adenosine as a possible mediator of metabolic control of glomerular filtration rate, Int. J. Biochem. 12:263–267.PubMedCrossRefGoogle Scholar
  10. Smellie, F.W., Davis, C.M., Daly, J.W. and Wells, J.N., 1979, Aklylxanthines. Inhibition of adenosine elicited accumulation of cyclic AMP in brain slices and of brain phosphodiesterase activity, Life Sci. 24:2475–2482.PubMedCrossRefGoogle Scholar
  11. Soll, A.H., 1980, Specific inhibition by prostaglandins E2 and I2 of histamine-stimulated [14C]aminopyrine accumulation and cyclic adenosine monophosphate generation by isolated canine parietal cells, J. Clin. Invest. 65:1222–1229.PubMedCrossRefGoogle Scholar
  12. Soil, A.H., 1982, Potentiating interactions of gastric stimulants on [14C]-aminopyrine accumulation by isolated canine parietal cells, Gastroenterology 83:216–223.PubMedGoogle Scholar
  13. Wollin, A., Soll, A.H. and Samloff, I.M., 1979, Actions of histamine, secretin, and PGE2 on cyclic AMP production by isolated canine fundic mucosal cells, Am. J. Physiol. 237:E437–E443.PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • J. G. Gerber
  • N. A. Payne

There are no affiliations available

Personalised recommendations