Distribution and characterization of vanilloid receptors in the rat stomach.
The cloned vanilloid receptor-1 (VR1) is recognized as a common molecular target for protons, noxious heat, and vanilloids. The presence of VR1 in the dorsal root, trigeminal, and nodose ganglia has been firmly established, but it is unclear in the gut, despite this VR1 may be important for gastric mucosal homeostasis. In this study we used an antibody and a radioligand to show the distribution of vanilloid receptors (VRs) in rat stomach and to characterize it. The deafferentiation of capsaicin-sensitive nerves in rats was induced by consecutive injections of capsaicin. VR1-immunopositive nerve endings were predominantly found in the mucous neck cells of the proliferation zone, and around blood vessels in the submucosa. Radioreceptor assay using [3H]-resiniferatoxin (RTX) revealed the existence of high affinity and single-class binding site in the membrane fractions of the mucosa. Capsaicin completely inhibited the specific binding of [3H]-RTX. Both the VR1 immunoreactivity and the receptor density of [3H]-RTX binding sites significantly reduced by the application of capsaicin for prolonged periods of time in the mucosa of rats. Our results indicate that VRs are expressed in the rat stomach, and suggest that they may be involved in mucosal protection by increasing cell proliferation and blood flow.
Nozawa
Y
Y
Pharmacology Research Laboratory, Taiho Pharmaceutical Company Limited, 224-2 Ebisuno, Hiraishi, Kawauchi-cho, 771-0194, Tokushima, Japan. nozawa-y@rb3.so-net.ne.jp
Nishihara
K
K
Yamamoto
A
A
Nakano
M
M
Ajioka
H
H
Matsuura
N
N
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001808:Blood Vessels / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D004224:Diterpenes / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D017615:Enteric Nervous System / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000294:innervation; D007150:Immunohistochemistry; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D013270:Stomach / Q000166:cytology / Q000187:drug effects / Q000294:innervation*; D013368:Submucous Plexus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014316:Tritium / Q000493:pharmacokinetics
D004224:Diterpenes; D011955:Receptors, Drug; D014316:Tritium; C024353:resiniferatoxin; D002211:Capsaicin