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Isolated guinea pig parietal cells, the function of which is similar to that of human parietal cells, were used in this study. The accumulation of 14C-aminopyrine (14C-AP) was measured to study the inhibitory mechanism of leminoprazole in cells. Stimulation by 10 microM histamine, 0.1 mM carbachol, 1 microM gastrin or 1 mM db-cAMP brought about satisfactory incorporation of 14C-AP, and leminoprazole concentration-dependently inhibited acid secretion induced by these stimulants. At 10(-5) M, almost 100% inhibition was observed. The IC50 values of leminoprazole obtained from its inhibitory action on histamine, carbachol, gastrin and db-cAMP-stimulated acid secretion were 4.0 x 10(-7) M, 3.5 x 10(-7) M, 2.5 x 10(-7) M and 5.6 x 10(-7) M, respectively. Thus the extent of inhibition was the same for the responses to all the secretagogues. These results indicate that the site of action of leminoprazole is intracellular and distal from cAMP (intracellular second messenger), but not at the receptor sites. The results also strongly suggest that the inhibitory action of leminoprazole on H+,K(+)-ATPase may contribute to the inhibitory effect of this drug on gastric acid secretion.

Inhibitory Effect of Leminoprazole on Acid Secretion in Parietal Cells Isolated from Guinea Pig Gastric Mucosa