Antisecretory activity of misoprostol, its racemates, stereoisomers and metabolites in isolated parietal cells.

Inhibition of histamine-stimulated acid secretion by misoprostol was compared to its racemates, stereoisomers and metabolites in isolated canine parietal cell preparations. The concentration of misoprostol required to inhibit 50% of maximal histamine-stimulated acid secretion (IC50) was 3.8 +/- 0.3 nM. One racemate of misoprostol was at least 1000 times more potent than the other. Of the four misoprostol stereoisomers, the 11R, 16S isomer exhibited the most potent activity against histamine with an IC50 value of 1.4 +/- 0.1 nM. The acid metabolite of misoprostol was equally potent as misoprostol. In contrast to the acid metabolite, the beta-oxidation metabolites of misoprostol lacked significant activity at 1 microM. The results indicate that: 1) the acid metabolite of misoprostol may play a significant role in the antisecretory activity of misoprostol, and 2) the high degree of stereo-specificity associated with the antisecretory effects indicates that the activity of misoprostol may be receptor mediated.