Induction of gastric lesions by 2-deoxy-D-glucose in rats following chemical ablation of capsaicin-sensitive sensory neurons.
Effects of chemical ablation of capsaicin-sensitive sensory nerves on functional and mucosal ulcerogenic responses to 2-deoxy-D-glucose (2DG) were investigated in the rat stomach, in comparison with those of indomethacin, a prostaglandin (PG) biosynthesis inhibitor. Intravenous injection of 2DG (200 mg/kg) followed by infusion of this agent (100 mg/kg/hr, i.v.) significantly increased gastric acid secretion and motility, but rarely induced macroscopic damage in the gastric mucosa of normal conscious rats. Chemical ablation of capsaicin-sensitive sensory nerves or pretreatment with indomethacin (5 mg/kg, s.c.) did not significantly affect the acid secretory and motility responses to 2DG, but induced severe hemorrhagic lesions in the stomach within 4 hr. Gastric mucosal blood flow (GMBF) determined by laser Doppler flowmetry under anesthetized conditions did not consistently change during 2DG treatment in any of these three groups, but the rise in GMBF in response to mucosal acidification (0.2 N HCl) was significantly inhibited in the animals pretreated with indomethacin or following chemical deafferentation. We conclude that functional ablation of capsaicin-sensitive sensory neurons, similar to the PG deficiency, increases the gastric mucosal vulnerability during 2DG infusion (acid hypersecretion and hypermotility due to vagal excitation), resulting in hemorrhagic lesions, and that the mechanism may be accounted for at least partly by the impairment of gastric mucosal blood flow response to mucosal acidification.
Matsumoto
J
J
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Ueshima
K
K
Ohuchi
T
T
Takeuchi
K
K
Okabe
S
S
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003714:Denervation; D003847:Deoxyglucose / Q000008:administration & dosage / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation; D005769:Gastrointestinal Motility / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D007275:Injections, Intravenous; D017078:Laser-Doppler Flowmetry; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D003847:Deoxyglucose; D002211:Capsaicin; D007213:Indomethacin