Prostacyclin inhibits gastric emptying and small-intestinal transit in rats and dogs

Abstract

Prostacyclin (PGI2) antagonizes 16,16-dimethyl prostaglandin E2-induced diarrhea in rats, presumably by inhibiting the fluid accumulation of “enteropooling” in the small intestine. The effect of PGI2 on gastric emptying, small intestinal transit, and colonic transit was examined in rats and dogs to determine if interference with propulsion might also contribute to the antidiarrheal properties of this compound. Rats implanted with chronic duodenal cannulas were given subcutaneous PGI2 (0.1–1000 μg/kg) followed 10 min later by intragastric 51Cr and a visually detectable duodenal transit marker. Forty-five minutes later, the animals were killed. Small-intestinal transit was expressed as the percentage of small intestinal length traveled by the visually detected marker. Gastric emptying was expressed as the percentage of the total 51Cr found in the small intestine. Subcutaneous PGI2 inhibited gastric emptying maximally at 10 μg/kg. Small-intestinal transit was significantly decreased at 50 μg/kg and almost completely suppressed at 1.0 mg/kg. Subcutaneous naloxone (0.5 mg/kg) given 10 min before and 20 min after subcutaneous PGI2 administration did not block PGI2's effects. Intravenous or oral PGI2 in doses as high as 0.2 or 10 mg/kg, respectively, had none of these effects. However, a high-dose intravenous bolus (1.0 mg/kg) or infusion (1.0 mg/kg · 45 min) both inhibited gastric emptying. Small intestinal transit was only decreased by PGI2 infusion, suggesting that this parameter was more sensitive to a sustained blood level than gastric emptying. Hourly injections of subcutaneous PGI2 (0.5 mg/kg) had no effect on rat colonic transit measured over a 3-h period after deposition of the transit marker through a colonic cannula in a manner similar to that described for small-intestinal transit above. Small-intestinal transit was also measured in dogs given a barium suspension through a chronic duodenal cannula. The animals simultaneously received subcutaneous PGI2 (10 μg/kg) and were given an additional treatment and an abdominal x-ray every 30 min thereafter. In vehicle-treated dogs, barium reached the cecal area in an average of 2.8 h after instillation. In PGI2-treated dogs, barium never reached the cecum in the 5-h examination period. Thus, PGI2 inhibits gastric emptying in rat and small-intestinal transit in rat and dog but has no effect on rat colonic transit. These properties could contribute to PGI2's antidiarrheal activity.