PGE2 mediates the effect of pentagastrin on intestinal adenylate cyclase and Na-K-ATPase activities.

The hypothesis that PGE2 mediates the effect of pentagastrin on jejunal Na-K-ATPase and adenylate cyclase activities was tested in rats. Mucosal PGE2 and cAMP contents, Na-K-ATPase and adenylate cyclase activities were determined 45 min after IV pentagastrin (1 microgram/100 g b.w.) administration to pyloric ligated rats. Pentagastrin almost doubled mucosal PGE2 content as compared to that in saline-treated rats: 198 +/- 19 (S.E., N = 11) and 109 +/- 9 (S.E., N = 26) pg/mg tissue, respectively, inhibited mucosal Na-K-ATPase activity: 16.4 +/- 0.7 (S.E., N = 8) as compared to 26.7 +/- 4.0 (S.E., N = 13) mumole/mg protein/h in saline-treated rats, stimulated adenylate cyclase activity by 146% and increased mucosal cAMP content by 80%. Pretreatment with indomethacin (4 mg/kg b.w., s.c./day x 2) prevented the increase in PGE2 content, the stimulation of adenylate cyclase activity and the inhibition of jejunal Na-K-ATPase activity induced by pentagastrin. The results reported thus suggest that the mechanisms whereby pentagastrin affects intestinal water and electrolyte transport are probably mediated by mucosal PGE2 and include inhibition of Na-K-ATPase activity and stimulation of the adenylate cyclase - cAMP system.