Induction of duodenal ulcers in sensory deafferented rats following histamine infusion.
We used capsaicin as a selective probe for sensory neuronal mechanisms and examined in rats whether defunctionalization of the sensory nerves caused duodenal ulcers in the presence of acid hypersecretion. Chemical deafferentation was performed by subcutaneous injection of capsaicin for 3 days (total dose: 100 mg/kg) 2 weeks before the experiment. This treatment did not cause by itself any damage in the duodenum. However, intravenous infusion of histamine (4, 8 and 16 mg/kg/h) in these animals caused hemorrhagic lesions in the proximal duodenum within 6 h in a dose-dependent manner with an incidence of 100%. Histamine alone in the control animals did not induce macroscopically visible lesions at lower doses and caused only slight damage at the highest dose (16 mg/kg/h), although acid secretion was stimulated to the maximal degree at 8 mg/kg/h. Ablation of capsaicin-sensitive sensory neurons did not have any effect on acid secretion induced by histamine (8 mg/kg/h), but significantly inhibited the increase in duodenal HCO3- secretion in response to mucosal acidification. We conclude that functional ablation of capsaicin-sensitive sensory nerves impairs duodenal HCO3- secretory response to acid and results in duodenal ulcers if acid hypersecretion is present. These sensory nerves may be important in the defense mechanism of the duodenum against luminal acid.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Matsumoto
J
J
Ueshima
K
K
Ohuchi
T
T
Okabe
S
S
D000818:Animals; D001639:Bicarbonates / Q000032:analysis; D002211:Capsaicin / Q000494:pharmacology; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D004386:Duodenum / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001639:Bicarbonates; D006632:Histamine; D002211:Capsaicin