Effect of cimetidine on ion fluxes and potential difference across the human stomach.
The H(2)-receptor antagonist, cimetidine, reduces acid output regardless of the means of stimulation. It is not known in man whether this is due entirely to a reduction in acid secretion or whether increased back diffusion of hydrogen ions is also occurring. We studied fluxes of H(+), Na(+), K(+), and Cl(-) ions after acid instillation into the human stomach in six healthy subjects with and without prior administration of 300 mg cimetidine orally. Potential difference across gastric mucosa was measured continuously throughout each study. Cimetidine caused a significant reduction in hydrogen ion secretion (5.05 mEq per 15 minutes controls versus 2.70 cimetidine, p &lt; 0.05), and consequently a significant reduction in net hydrogen flux into the gastric lumen (2.01 mEq per 15 minutes versus 0.02, p &lt; 0.05). There were no significant differences between sodium ion fluxes in control and cimetidine studies, suggesting that the gastric mucosal barrier remained intact. Cimetidine alone caused a highly significant rise in intragastric pH (to 7) and of potential difference (p &lt; 0.001). Addition of intragastric acid (pH &lt; 1.0) did not reverse the rise in potential difference caused by cimetidine, suggesting that factors other than change in intragastric pH were involved. In conclusion, our studies support the concept that reduction in acid output by cimetidine is due to inhibition of acid secretion, and not to increased permeability to hydrogen ion.
Effect of cimetidine on ion fluxes and potential difference across the human stomach. The H(2)-receptor antagonist, cimetidine, reduces acid output regardless of the means of stimulation. It is not known in man whether this is due entirely to a reduction in acid secretion or whether increased back diffusion of hydrogen ions is also occurring. We studied fluxes of H(+), Na(+), K(+), and Cl(-) ions after acid instillation into the human stomach in six healthy subjects with and without prior administration of 300 mg cimetidine orally. Potential difference across gastric mucosa was measured continuously throughout each study. Cimetidine caused a significant reduction in hydrogen ion secretion (5.05 mEq per 15 minutes controls versus 2.70 cimetidine, p &lt; 0.05), and consequently a significant reduction in net hydrogen flux into the gastric lumen (2.01 mEq per 15 minutes versus 0.02, p &lt; 0.05). There were no significant differences between sodium ion fluxes in control and cimetidine studies, suggesting that the gastric mucosal barrier remained intact. Cimetidine alone caused a highly significant rise in intragastric pH (to 7) and of potential difference (p &lt; 0.001). Addition of intragastric acid (pH &lt; 1.0) did not reverse the rise in potential difference caused by cimetidine, suggesting that factors other than change in intragastric pH were involved. In conclusion, our studies support the concept that reduction in acid output by cimetidine is due to inhibition of acid secretion, and not to increased permeability to hydrogen ion.