Determination of acid-neutralizing capacity in rat duodenum. Influences of 16,16-dimethyl prostaglandin E2 and nonsteroidal antiinflammatory drugs.
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 X 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 (approximately 9 mu eq/hr). Subcutaneous administration of 16,16-dmPGE2 (10 micrograms/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 (approximately 5 mu eq/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.(ABSTRACT TRUNCATED AT 250 WORDS)
K
K
Takeuchi
O
O
Furukawa
H
H
Tanaka
S
S
Okabe
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D001639:Bicarbonates; D011459:Prostaglandins E, Synthetic; D011796:Quinacrine; D015064:16,16-Dimethylprostaglandin E2; D001241:Aspirin; D007213:Indomethacin