Inhibitory mechanism of oxethazaine on release of endogenous secretin and pancreatic response in dogs.

The mechanism by which oxethazaine inhibits hydrochloric acid stimulation of pancreatic secretion and the endogenous release of secretin was studied in six dogs prepared with pancreatic and gastric fistulae. Oxethazaine reduced both pancreatic secretion and plasma secretin concentration evoked by duodenal acidification, and the degree of inhibition was proportional to its dose. This drug did not inhibit the pancreatic secretion stimulated by the exogenous secretin. From kinetic analyses, it seems that oxethazaine acted as noncompetitive inhibitor of hydrogen ion on the chemoreceptors of the secretin-releasing cells in the duodenal mucosa. This may result in a decrease of secretin release from these cells and consequently of pancreatic secretion.