The Role of Adenosine on the Gastric Acid Secretory Response

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

Abstract

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.

Keywords

Adenosine Histamine Caffeine Indomethacin Theophylline 

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References

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Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • J. G. Gerber
  • N. A. Payne

There are no affiliations available

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