Determination of acid-neutralizing capacity in rat duodenum

Abstract

A model involving measurement of duodenal pH and acid-neutralizing capacity has been devised in anesthetized rats. A duodenal loop was made between the pyloric ring and the area just proximal to the outlet of the common bile duct (2 cm) and was perfused at a flow rate of 1.3 ml/min with HCl solution (1×10⁻⁴ M, pH 4.0) made isotonic with NaCl. The pH of duodenal perfusate was continuously measured using a pH glass electrode of the flow type, and the amount of acid neutralized in the loop was titrated to pH 4.0 using a pH-stat method and by adding 10 mM HCl. Under normal conditions, the duodenal pH was kept around 6.0 as the result of neutralization in the loop (∼9 μeq/hr). Subcutaneous administration of 16,16-dmPGE₂ (10 μg/kg) significantly elevated the pH and increased acid-neutralizing capacity to 168.3% of normal levels. In contrast, indomethacin (5 mg/kg) and aspirin (200 mg/kg) as cyclooxygenase inhibitors or quinacrine (100 mg/kg) as a phospholipase A₂ inhibitor significantly decreased both the pH and acid neutralizing capacity. After sacrifice with saturated KCl (intravenously), the pH decreased to 4.3±0.2 and the neutralizing capacity was reduced to 30% of normal values. Basal HCO₃ ⁻ secretion in the proximal duodenum (∼5 μeq/hr), when titrated to pH 7.4, was significantly stimulated by 16,16-dmPGE₂ and exposure of the mucosa for 10 min to 10 mM HCl. Neither indomethacin, aspirin, nor quinacrine had any effect on basal HCO₃ ⁻ secretion, but all significantly inhibited HCl-stimulated HCO₃ ⁻ secretion. These results suggest that endogenous prostaglandins play an important role in maintaining acid neutralizing capacity in the duodenum. The present system could be useful for screening drugs which may influence acid neutralizing capacity in the duodenum and for investigating the mechanisms of duodenal HCO₃ ⁻ secretion underin vivo conditions.