Interaction between prostaglandins and cyclic AMP in the gastric mucosa
Soll, A.H.; Whittle, B.J.
Prostaglandins 21 Suppl: 39-45
1981
ISSN/ISBN: 0090-6980 PMID: 6272369 DOI: 10.1016/0090-6980(81)90115-5
Accession: 028555440
Possible mechanisms accounting for the inhibition of acid secretion by prostaglandins were studied using cells dispersed from canine fundic mucosa by enzymes and enriched in the content of parietal cells by elutriation. The accumulation of 14C-aminopyrine (AP) was used as an index of parietal cell response to stimulation. PGE2 inhibited histamine-stimulated Ap uptake, with 50% inhibition (ID50) found at 10 n M, but did not block the response to carbachol, gastrin, or dibuturyl cyclic AMP. PGE2 did, however, inhibit aminopyrine uptake stimulated by carbachol and gastrin when the response to these agents was potentiated by histamine. PGE2, at namomolar concentrations, also inhibited histamine-stimulated cyclic Amp production. When mucosal cells were treated with only PGE2 at concentrations above 1 μM, stimulation of cyclic Amp production was found. In cell separation studies with the elutriator rotor, PGE2 appeared to stimulate cyclic Amp production primarily in nonparietal cells. Prostacyclin (PGI2) and two stable analogues, 6β-PGI1 and the 16-phenoxy analogue (5α)5,9-epoxy-16-phenoxy-PGF1, also specifically inhibited histamine-stimulated Ap accumulation. PGI2 required relatively high concentrations for this effect (ID50 = 1 μM), whereas the 16 phenoxy derivative was much more potent in its inhibition of histamine-stimualted Ap accumulation (ID50 = 10 n M), with this difference probably accounted for by the rapid degradation of PGI2 compared to the stable 16-phenoxy analogue. All three of these prostanoids also inhibited histamine-stimulated cyclic Amp production. As was found with PGE2, at high concentrations and in the absence of histamine PGI2 and PGI1 also stimulated cyclic Amp production. However, the 16-phenoxy analogue failed to stimulate cyclic Amp production either in the parietal cell enriched fractions or in the nonparietal cell fractions. These data indicate that PGE2 and prostacyclin analogues are potent, direct and specific 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 the prostanoid compounds.