Effect of 1-phenylpentanol on release of secretin and exocrine pancreatic secretion in dogs and humans

Abstract

1-Phenyl-1-hydroxy-N-pentane is a synthetic derivative of an ingredient of Curcuma longa that is used as a condiment and dye. The effects of 1-phenyl-1- hydroxy-N-pentane on release of secretin, gastrin, and pancreatic secretion of bicarbonate and protein were studied in both dogs and humans. In fasting dogs with gastric fistulas and modified Herrera's pancreatic fistulas, intraduodenal administration of 1-phenyl-1-hydroxy-N-pentane (pH 6.7) in three different doses (25, 50, and 100 mg/kg) resulted in significant increases in both plasma secretin concentration and bicarbonate output. The increases in the two variables were dose related. The bicarbonate output and plasma secretin concentration produced by the doses of 1-phenyl-1-hydroxy-N-pentane correlated well. No significant change occurred in either protein output or plasma gastrin concentration. The effect of intragastric 1-phenyl-1-hydroxy-N-pentane on release of secretin and pancreatic secretion was also studied in the digestive state. While gastric pH was maintained at 5.5 by intragastric titration with 1 N NaOH after intragastric administration of 5% liver extract solution, intragastric administration of 1-phenyl-1-hydroxy-N-pentane (100 mg/kg) resulted in significant increases in both plasma secretin concentrations and pancreatic bicarbonate output. In the same experiment, the plasma gastrin concentration did not change significantly, whereas gastric acid secretion decreased significantly after the 1-phenyl-1-hydroxy-N-pentane administration. In 6 human volunteers, both plasma secretin concentration and pancreatic bicarbonate output significantly increased when 2% 1-phenyl-1-hydroxy-N-pentane solution, 30 ml/30 min, was infused in the upper jejunum. Again, no increase in the protein output was apparent. These studies indicate that endogenous secretin is released by an agent other than acid and suggest strongly that the increased pancreatic bicarbonate secretion is attributed to the increased plasma concentration of secretin. 1-Phenyl-1-hydroxy-N-pentane may be a useful agent for release of secretin in subjects with achlorhydria, severe hyposecretory state, or total gastrectomy.