Prostacyclin analogues inhibit canine parietal cell activity and cyclic AMP formation

To assess further the mechanism by which prostacyclin inhibits acid secretion, the actions of two stable prostacyclin analogues on parietal cell function and cyclic AMP formation were tested using enzymatically dispersed cells from canine fundic mucosa. Accumulation of 14C-aminopyrine (AP) was used as an index of parietal cell response to stimulation. The 16-phenoxy derivative or PGI2 inhibited accumulation of AP stimulated by histamine (10 microM), with 50% inhibition (ID50) at 10 nM. 68-PGI1 also inhibited the action of histamine (ID50 0.5 microM) but failed to block stimulation by carbachol or the dibutyryl derivative of cyclic AMP (dbcAMP). In similar concentrations to those producing inhibition of histamine-stimulated AP accumulation, the 16-phenoxy analogue and 6 beta-PGI1 inhibited histamine-stimulated cyclic AMP generation by parietal cells. At 100 fold higher concentrations, 68-PGI1 stimulated cyclic AMP formation, presumably in non-parietal cells. Even in high concentrations the 16-phenoxy analogue failed to increase cyclic AMP formation by mucosal cells. These data indicate that the stable prostacyclin analogues are potent, direct inhibitors of histamine-stimulated parietal cell function and that it is the inhibition, rather than the stimulation, of cyclic AMP formation that is linked to the antisecretory actions of these prostanoid compounds.