The role of accelerated colonic transit in prostaglandin-induced diarrhoea and its inhibition by prostacyclin.

Rats treated with subcutaneous 16,16-dimethyl prostaglandin E2 (16,16-dimethyl PGE2, 100 micrograms kg-1) exhibited diarrhoea even when their ileo-caecal junctions were tied, thereby eliminating contributions from small intestinal transit or fluid accumulation (enteropooling). The origin of the watery stool appeared to be the caecum, since tying the caecal-colonic junction eliminated it. The acceleration of colonic transit is likely to be a primary mechanism of PGE2-induced diarrhoea in the rat, since both normal animals and those with tied ileo-caecal junctions exhibited almost the same incidence of diarrhoea. Subcutaneous prostacyclin (PGI2) (2 mg kg-1 every 60 min) suppressed 16,16-dimethyl PGE2-induced diarrhoea in normal rats and in those with tied ileo-caecal junctions. Colonic transit measured in rats with cannula preimplanted in their proximal colon indicated that 16,16-dimethyl PGE2 enhanced colonic transit and PGI2 suppressed this increase. Thus, PGI2 can inhibit diarrhoea in the rat caused by 16,16-dimethyl PGE2 by suppressing colonic transit exclusive of its effects on small intestinal transit and enteropooling.