Release of prostaglandin E2 into gastric juice during stimulation of muscarinic- and gastrin receptors in dogs and in humans.
To investigate the causal relationship, if any, between gastric PG formation and gastric acid output, the release of PGE2 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 PGE2 was determined by a method validated by gas chromatography-mass spectrometry and PGE2 values were normalized by expressing them as ng PGE2 released per meq H+ secreted. In the dogs "steady state" PGE2 output (0.4-10 ng/meq H+) was interrupted during continuous 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 less than 0.01) higher (3.9-46 ng/meq H+) than in pentagastrin experiments (0.8-20 ng/meq H+). In humans the peak PGE2 output during sham feeding (3.4-41 ng/meq H+) was significantly (p less than 0.02) larger than following bolus stimulation (6/micrograms/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 PGE2 output were preceded by increased myoelectrical activity (i.e. mean contractile index).
D000328:Adult; D000368:Aged; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology*; D015232:Dinoprostone; D004285:Dogs; D004381:Duodenal Ulcer / Q000503:physiopathology; D005260:Female; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010418:Pentagastrin / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D011949:Receptors, Cholecystokinin; D011950:Receptors, Cholinergic / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*
D001626:Bethanechol Compounds; D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D018723:Bethanechol; D010418:Pentagastrin; D015232:Dinoprostone