Gastric hyperemic response induced by acid back-diffusion in rat stomachs following barrier disruption -- relation to vanilloid type-1 receptors.
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).


METHODS
Under urethane anesthesia, a rat stomach was mounted on an ex-vivo chamber, perfused with 50 mM HCl, and changes in PD, gastric mucosal blood flow (GMBF), and luminal acid loss were measured before and after exposure to 20 mM TC for 30 min, in presence of omeprazole. Capsazepine was co-applied with 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 minimal damage in the mucosa. Chemical ablation of CSN attenuated the GMBF response to TC without affecting PD reduction and acid loss, and resulted in severe lesions, while none of these responses induced by TC was 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 of action differ in terms of capsazepine- or ruthenium red-sensitivity. Although the luminal H+ plays a modulator role for the physiological response mediated by CSN in the stomach, it is unlikely that the action results from the interaction of H+ with the capsazepine- or ruthenium red-sensitive site of VR1.
Tashima
Kimihito
K
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
Nakashima
Masato
M
Kagawa
Shigeru
S
Kato
Shinichi
S
Takeuchi
Koji
K
D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004058:Diffusion; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D006859:Hydrogen / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism*; D012430:Ruthenium Red / Q000494:pharmacology; D013270:Stomach / Q000473:pathology*; D013276:Stomach Ulcer / Q000139:chemically induced*; D050916:TRPV Cation Channels; D013656:Taurocholic Acid / Q000494:pharmacology; D013997:Time Factors
D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D012430:Ruthenium Red; D013656:Taurocholic Acid; D006859:Hydrogen; C071423:capsazepine; D002211:Capsaicin