Stimulation of gastric alkaline secretion by stable prostacyclin analogues in rat and dog.
The stimulation of gastric alkaline secretion in vivo following topical mucosal application of four stable anti-ulcer analogues of prostacyclin has been investigated in the rat and in the dog using intragastric pH-stat techniques. In the rat, basal alkaline secretion was significantly stimulated by the prostacyclin analogues 16-phenoxy-(5 alpha)-5,9-epoxy-PGF1 (16-phenoxy) and its methyl ester, when administered in the luminal perfusion fluid. The 16-phenoxy analogue (25 and 50 micrograms ml-1) increased basal alkaline secretion with its methyl ester being more potent. The methyl ester of 16,16-dimethyl PGI1 (25 and 50 micrograms ml-1) likewise stimulated alkaline secretion whereas its corresponding free acid was inactive at these concentrations. In further studies in the conscious dog with a Heidenhain gastric pouch, these four prostacyclin analogues administered intraluminally (1.25 micrograms ml-1) significantly increased gastric alkaline secretion. The present findings indicate that the stable 16-phenoxy and 16, 16-dimethyl analogues of prostacyclin, can stimulate gastric alkaline secretion in the dog and rat in vivo. As with the previously reported 16,16-dimethyl PGE2 analogue, this property of stimulating alkaline secretion may therefore contribute to the antiulcer activity of these prostacyclin analogues.
D000468:Alkalies / Q000378:metabolism; D000818:Animals; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology*; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D000468:Alkalies; D011464:Epoprostenol