Role of local motility changes in the pathogenesis of duodenal ulcers induced by cysteamine in rats.
The possible role of local motility in the pathogenesis of duodenal ulcers was investigated in rats using cysteamine. Duodenal motor activity was measured as intraluminal pressure recordings by means of a balloon positioned in the proximal duodenum. Subcutaneous administration of cysteamine (100 mg/kg) produced two linear bandlike lesions in the proximal duodenum within 6 hr. This dose of cysteamine significantly increased gastric acid secretion in acute fistula rats, and decreased duodenal HCO3- secretion caused by acid. During this period, this agent inhibited gastric motility but did produce markedly enhanced contractions in the duodenum. The changes in duodenal motility appeared within 5-10 min and were dose-dependent for cysteamine (10-100 mg/kg). Pretreatment with subcutaneously administered atropine (10 mg/kg), 16,16-dmPGE2 (30 micrograms/kg) or dopamine (10 or 30 mg/kg) significantly reduced the development of duodenal lesions caused by cysteamine, the inhibition being 86.8%, 49.7%, 54.5% or 67.8%, respectively. In the presence of cysteamine, dopamine had minimal effect on both acid and HCO3- secretion, while atropine or 16,16-dmPGE2 markedly inhibited acid secretion or increased HCO3- secretion, respectively. The enhanced duodenal motility induced by cysteamine was blocked partially by atropine and only slightly by 16,16-dmPGE2. Dopamine showed a dose-dependent inhibition on the duodenal hypermotility following cysteamine, and at 30 mg/kg almost completely abolished the development of contractions. These results suggest that abnormal hypermotility in the duodenum may be partly involved in the pathogenesis of cysteamine-induced duodenal ulcers.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003543:Cysteamine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000209:etiology*; D004386:Duodenum; D005745:Gastric Acidity Determination; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007419:Intestinal Secretions / Q000032:analysis / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D003543:Cysteamine; D001285:Atropine; D015064:16,16-Dimethylprostaglandin E2; D004298:Dopamine