Release of prostaglandin E 2 into gastric juice during stimulation of muscarinic- and gastrin receptors in dogs and in humans

Abstract

To investigate the causal relationship, if any, between gastric PG formation and gastric acid output, the release of PGE 2 into gastric juice has been studied in eight beagle dogs with a gastric fistula, using sustained half-maximal stimulation by bethanechol and pentagastrin, and in eight duodenal ulcer patients, using the combined sham feeding/pentagastrin test. Immunoreactive PGE 2 was determined by a method validated by gas chromatography-mass spectrometry and PGE 2 values were normalized by expressing them as ng PGE 2 released per meq H + secreted. In the dogs “steady state” PGE 2 output (0.4–10 ng/meq H +) was interrupted during continous i.v. pentagastrin infusion by symmetrical peaks (50–60 minutes of duration) with a maximum of 24±3.1 ng/meq H + (mean±SEM). During bethanechol stimulation the rhythmic variations were smaller, but the median values for the periods 30 to 180 or 240 minutes significantly ( p < 0.01) higher (3.9–46 ng/meq H +) than in pentagastrin experiments (0.8–20 ng/meq H +). In humans the peak PGE 2 output during sham feeding (3.4–41 ng/meq H +) was significantly ( p < 0.02) larger than following bolus stimulation (6 ug/kg) by pentagastrin (2.2–18 ng/meq H +). The findings are consistent with the hypothesis that activation of muscarinic receptors represents the physiologic mechanism by which gastric release of PGs is regulated. Cyclic variations in gastric PG formation appear to occur in response to vagal stimulation since the peaks in PGE 2 output were preceeded by increased myoelectrical activity (i.e. mean contractile index).