Desensitization of capsaicin-sensitive sensory neurons in rat stomachs on chronic treatment with sodium taurocholate.
We examined the effects of chronic treatment with 10 mM sodium taurocholate (TC) on gastric functions, capsaicin-sensitive afferent neurons and the gastric mucosa in male rats. Stomachs were mounted in Lucite chambers, and then the transmucosal potential difference (PD), luminal pH and gastric mucosal blood flow (GMBF) in response to TC or capsaicin was determined. In normal animals, 10 mM TC caused a reduction in PD, and increases in luminal pH and GMBF. Capsaicin (1 mg/ml) produced an apparent increase in GMBF without any change in PD or luminal pH. After 4- or 12-week treatment with TC, the basal PD was significantly reduced, and the luminal pH tended to increase. The increase in GMBF in response to TC or capsaicin was profoundly suppressed in TC-pretreated animals. The calcitonin gene-related peptide release in response to capsaicin was significantly reduced after 4 weeks treatment with TC. There were no microscopical changes in the oxyntic mucosa until 4 weeks after TC treatment except for exfoliation of surface cells. However, an increase in inflammatory cell infiltration was observed 12 weeks later. We conclude that chronic treatment with TC causes desensitization of capsaicin-sensitive afferent neurons and reduces GMBF, which may result in the production of gastritis.
Narita
M
M
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Takahashi
S
S
Takeuchi
K
K
Okabe
S
S
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013194:Staining and Labeling; D013656:Taurocholic Acid / Q000494:pharmacology*
D013656:Taurocholic Acid; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin