Influence of a synthetic prostaglandin analog on pancreatic secretion

Effects of a synthetic prostaglandin analog-16--16-dimethyl prostaglandin E2, methyl ester (16-diMe-PGE2)--on pancreatic secretion were evaluated in seven dogs with chronic duodenal fistulas. Graded doses of 16-diMe-PGE2 were administered intravenously (0.1, 0.3, 0.5, and 1.0 mug per kilogram, intraduodenally, or intragastrically (15, 30, 50, 100 mug per kilogram) with the pancreas in the resting state or in response to (1) secretin and (2) secretin with cholecystokinin-pancreozymin. Profound and prolonged inhibition of volume and bicarbonate concentration of secretion occurred in the resting and stimulated gland. ED50 was 0.31 mug per kilogram intravenously (1/75 the ED50 for PGE1) and 25 mug per kilogram intraduodenally. As with PGE1, stimulation of enzymes occurred, even with doses that were subthreshold for inhibition of volume and HCO3. Like PGE1, 16-diMe-PGE2 has a dual action on the intact canine pancreas (stimulation of enzymes and inhibition of volume and electrolytes), but is much more potent, has a prolonged action, and is active intraduodenally and intragastrically. Nonsteroid inhibitors of endogenous prostaglandin synthesis did not alter these effects.