Exogenous and endogenous acid and pepsins in the pathogenesis of duodenal ulcers in the rat.
A continuous subcutaneous infusion for 24 hr of the gastric secretagogues, pentagastrin (4 micrograms/kg/min) together with carbachol (0.8 micrograms/kg/min) produced a 100% incidence of duodenal ulcers (DU) in male albino Wistar rats. The mean acid output producing these duodenal ulcers was 2.3 mmol/24 hr, with a gastric secretory volume of 25 (+/- 1) ml/24 hr at an acid concentration of 91 (+/- 2) mmol/liter. The pepsin activity in the gastric juice was 185 micrograms/ml. To simulate this acid-pepsin hypersecretion, acid and/or pepsin was infused intragastrically for 24 hr. The intragastric infusion of hydrochloric acid (0.1 M, 0.2 M, 0.5 M) alone and hog purified pepsin (2.5, 5, 10 mg/24 hr) at a constant rate of 1 ml/hr for 24 hr failed to produce duodenal ulcers in rats although gastric lesions in the body of the stomach were produced. The infusion of 0.2 M HCl with 5 mg pepsin over 24 hr produced DU in two of 10 rats. However, pooled secretagogue-stimulated gastric juice, infused intragastrically, produced DUs in 11 of 12 rats. Acid alone does not produce DU experimentally in rats at the rate of infusion used in these experiments. Acid and exogenous procine pepsin (similar to human pepsin 3 on agar gel electrophoresis) rarely produced duodenal ulcers. However, acid and endogenous rat pepsin are needed together for the duodenal ulcerogenesis. This pepsin may be an obligatory ulcerogenic factor in the rat.
D000818:Animals; D002217:Carbachol / Q000008:administration & dosage / Q000009:adverse effects*; D004357:Drug Synergism; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000209:etiology*; D005750:Gastric Juice / Q000378:metabolism*; D006728:Hormones / Q000008:administration & dosage / Q000009:adverse effects; D007263:Infusions, Parenteral; D008297:Male; D010418:Pentagastrin / Q000008:administration & dosage / Q000009:adverse effects*; D010434:Pepsin A / Q000378:metabolism*; D051381:Rats; D013268:Stimulation, Chemical
D006728:Hormones; D002217:Carbachol; D010434:Pepsin A; D010418:Pentagastrin