Production by Secretagogues of Duodenal Ulcers in the Rat

Duodenal ulcers were produced in rats by subcutaneous infusion for 48 hr of either of the following secretagogues: histamine, carbachol, pentagastrin. When any two of these secretagogues were administered together, synergism was observed in the ulcerogenic effect. Synergism, or potentiation, is defined as an effect produced by two agents given together that is greater than the sum of the effects produced by each agent when given separately. The ulcers were located opposite to the mesenteric attachment, were often multiple, and extended as far as 4 cm from the pylorus. Their severity ranged from shallow erosions to perforation with peritonitis. When two secretagogues were infused at the same time, the incidence of animals with ulcers, their severity, number, and distance from the pylorus were related to the doses given. Pentagastrin, when administered alone, was the least ulcerogenic agent, but when pentagastrin was given with either histamine or carbachol, the ulcerogenic effect was potentiated. Although the duodenum was consistently ulcerated, the stomach remained intact, except in some animals receiving high doses of secretagogues and dying or dead from peritonitis. It is concluded that: (1) the rat can develop duodenal ulcers; and (2) secretagogues, when infused for 48 hr and especially when combined, can produce such ulcers; (3) the mechanism by which these ulcers develop remains to be elucidated.