Gastric hyperemic response induced by acid back-diffusion in rat stomachs following barrier disruption - relation to vanilloid type-1 receptors.
Masato Nakashima, Shigeru Kagawa, Kimihito Tashima, Shinichi Kato, Koji Takeuchi
Med Sci Monit 2002; 8(5): BR157-163
BACKGROUND: Acid back-diffusion activates capsaicin-sensitive sensory neurons(CSN), leading to gastric hyperemic response. We examined the role of vanilloid type-1 receptor (VR1)in gastric hyperemic and ulcerogenic responses in rat stomach following exposure to taurocholate (TC).MATERIAL/METHODS: Under urethane anesthesia, a rat stomach was mounted on an ex-vivo chamber, perfusedwith 50 mM HCl, and changes in PD, gastric mucosal blood flow (GMBF), and luminal acid loss were measuredbefore and after exposure to 20 mM TC for 30 min, in presence of omeprazole. Capsazepine was co-appliedwith TC for 30 min to the stomach, while ruthenium red was given i.v. 10 min before TC treatment. RESULTS:TC caused a marked PD reduction, followed by an increase of acid loss and GMBF, resulting in minimaldamage in the mucosa. Chemical ablation of CSN attenuated the GMBF response to TC without affecting PDreduction and acid loss, and resulted in severe lesions, while none of these responses induced by TCwas significantly affected by either capsazepine or ruthenium red. Intragastric capsaicin increased GMBF,and this response was attenuated by both capsazepine and ruthenium red as well as sensory deafferentation.CONCLUSIONS: Both acid back-diffusion and capsaicin increase GMBF mediated by CSN, yet their modes ofaction differ in terms of capsazepine- or ruthenium red-sensitivity. Although the luminal H+ plays amodulator role for the physiological response mediated by CSN in the stomach, it is unlikely that theaction results from the interaction of H+ with the capsazepine- or ruthenium red-sensitive site of VR1.
Keywords: Animals, Capsaicin, Diffusion, Gastric Acid, Gastric Mucosa, Hydrogen, Rats, Rats, Sprague-Dawley, Receptors, Drug, Ruthenium Red, Stomach, stomach ulcer, Taurocholic Acid, Time Factors