Inhibition of gastric secretion in the dog by 16,16-dimethyl prostaglandin E2

The synthetic prostaglandin 16,16-dimethyl E2 (PGE2) given by intravenous infusion at 0.4 mug/kg-h inhibited gastric secretion of H+, K+, Cl-, and pepsin in four fistula dogs stimulated by histamine (H), pentagastrin (P), urecholine (U), and 2-deoxy-D-glucose (2-DG). When given for 90 min during steady infusions of near-maximal doses of H, P, and U, PG-E2 caused 75% inhibition of H+ maximally at 90 min and over 85% inhibition of pepsin secretion maximally at 45 min. Recovery of secretion took 1-2 h after infusion of PGE2 was stopped. Injection of KCl, 1 meq/kg, during inhibition of histamine by PGE2 gave only a 15-min transient reversal in inhibition. When PGE2 was given as background to 45-min step-dose responses, 0.1 mug/kg competitively inhibited histamine stimulation and 0.4 mug/kg-h gave 100% inhibition. Against pentagastrin, 0.1 mug PGE2/kg-h had no effect and 0.4 mug caused uncompetitive inhibition; against urecholine, 0.4 mug PGE2/kg-h caused competitive inhibition of H+ secretion. Pepsin was more markedly inhibited in each case. There were no side effects at either dose of PGE2, which is a potent inhibitor of gastric secretion with all forms of stimuli.