Localization of TRPV1 and contractile effect of capsaicin in mouse large intestine: high abundance and sensitivity in rectum and distal colon.
We investigated immunohistochemical differences in the distribution of TRPV1 channels and the contractile effects of capsaicin on smooth muscle in the mouse rectum and distal, transverse, and proximal colon. In the immunohistochemical study, TRPV1 immunoreactivity was found in the mucosa, submucosal, and muscle layers and myenteric plexus. Large numbers of TRPV1-immunoreactive axons were observed in the rectum and distal colon. In contrast, TRPV1-positive axons were sparsely distributed in the transverse and proximal colon. The density of TRPV1-immunoreactive axons in the rectum and distal colon was much higher than those in the transverse and proximal colon. Axons double labeled with TRPV1 and protein gene product (PGP) 9.5 were detected in the myenteric plexus, but PGP 9.5-immunoreactive cell bodies did not colocalize with TRPV1. In motor function studies, capsaicin induced a fast transient contraction, followed by a large long-lasting contraction in the rectum and distal colon, whereas in the transverse and proximal colon only the transient contraction was observed. The capsaicin-induced transient contraction from the proximal colon to the rectum was moderately inhibited by an NK1 or NK2 receptor antagonist. The capsaicin-induced long-lasting contraction in the rectum and distal colon was markedly inhibited by an NK2 antagonist, but not by an NK1 antagonist. The present results suggest that TRPV1 channels located on the rectum and distal colon play a major role in the motor function in the large intestine.
Matsumoto
Kenjiro
K
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8555, Japan. kenjiro@jiu.ac.jp
Kurosawa
Emi
E
Terui
Hiroyuki
H
Hosoya
Takuji
T
Tashima
Kimihito
K
Murayama
Toshihiko
T
Priestley
John V
JV
Horie
Syunji
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism; D015288:Neurokinin A / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000378:metabolism; D012007:Rectum / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000032:analysis
C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D011719:Pyrazines; D011725:Pyridines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D013373:Substance P; D013779:Tetrodotoxin; D001285:Atropine; D015288:Neurokinin A; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse; D002211:Capsaicin