Capsaicin-sensitive sensory nerves in recovery of gastric mucosal integrity after damage by sodium taurocholate in rats.
We compared the recovery process of gastric mucosal integrity after damage by 20 mM sodium taurocholate (TC) in control, sensory deafferented and indomethacin-treated rats. Under anesthetized conditions, the stomach was mounted on a chamber and perfused with saline or 50 mM HCl. Application of TC (30 min) to the saline-perfused stomach produced a marked reduction in the potential difference (PD) (surface epithelial damage), followed by increases of gastric mucosal blood flow (GMBF) and luminal pH (alkalinization), but there was a rapid recovery of PD without development of gross lesions. Chemical ablation of capsaicin-sensitive sensory nerves had no influence on the PD reduction and luminal alkalinization, but significantly inhibited the rise in GMBF and the PD recovery. Indomethacin pretreatment (5 mg/kg, s.c.) significantly inhibited these changes seen after exposure to TC, except for PD reduction. In contrast, TC caused a sizable amount of H+ back-diffusion and a more pronounced and persistent rise in GMBF in the stomach perfused with 50 mM HCl, yet only minimal damage was observed in the control animals. Under these conditions, both sensory deafferentation and indomethacin inhibited such GMBF responses, leading to hemorrhagic damage without affecting the degree of H+ back-diffusion. These results suggest that capsaicin-sensitive sensory nerves contribute to the recovery of gastric mucosal integrity after damage, probably by maintaining GMBF responses associated with H+ back-diffusion and preventing the later extension to gross damage in the presence of acid.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Ohuchi
T
T
Narita
M
M
Okabe
S
S
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D003714:Denervation; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013656:Taurocholic Acid / Q000633:toxicity*
D013656:Taurocholic Acid; D002211:Capsaicin; D007213:Indomethacin