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Inhibitory Effects of Histamine H2-Antagonists on Forskolin-Stimulated Acid Production in Isolated Parietal Cells

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Summary

The effect of the histamine H2-antagonists cimetidine and ranitidine on aminopyrine accumulation stimulated by forskolin was investigated in isolated guinea pig parietal cells. Forskolin (10−5mol/L) caused a 2.2-fold increase in acid production, assessed as [14C]-aminophenazone (aminopyrine) accumulation, and a 19-fold increase in cyclic AMP. The H2-antagonists 10−4 mol/L) almost completely inhibited the forskolin-induced aminopyrine accumulation, without affecting the cyclic AMP level. Histamine released by forskolin from contaminated cells into the media was 5.08 ± 0.28 × 10−8 mol/L, which was not sufficient to stimulate acid secretion in parietal cells. Therefore, it is suggested that the H2-antagonists may inhibit acid secretion at the step subsequent to the synthesis of cyclic AMP, in addition to antagonism of the histamine receptors.

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Correspondence to Dr Tadao Itoh.

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Ishikawa, T., Kamisaki, Y., Omodani, H. et al. Inhibitory Effects of Histamine H2-Antagonists on Forskolin-Stimulated Acid Production in Isolated Parietal Cells. Drug Invest 2, 38–43 (1990). https://doi.org/10.1007/BF03259400

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Keywords

  • Histamine
  • Cimetidine
  • Ranitidine
  • Adenylate Cyclase
  • Forskolin