Effect of colchicine on jejunal adenylate cyclase activity, PGE2 and cAMP contents.

The effect of colchicine on jejunal adenylate cyclase activity, prostaglandin E2 (PGE2) and cAMP contents, the enzyme and mediators involved in intestinal fluid secretion was tested in rats. Four h after the intraperitoneal injection of colchicine (0.5 mg/100 g body wt.) mucosal PGE2 content, adenylate cyclase activity and mucosal cAMP content were almost doubled. Pretreatment with indomethacin (4 mg/kg body wt., s.c./day x 2) or methyl prednisolone (3.0 mg/kg body wt.) decreased both the increase in mucosal PGE2 content and the stimulation of adenylate cyclase activity induced by colchicine. These results suggest that the stimulation of adenylate cyclase activity and an increase in mucosal PGE2 and cAMP contents might be among the mechanisms whereby colchicine induces a net accumulation of water manifested clinically as diarrhea. It is also suggested that the stimulation of adenylate cyclase activity is mediated by the increase in mucosal PGE2 content.