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NEUROREGULATION AND MOTILITY

Localization of TRPV1 and contractile effect of capsaicin in mouse large intestine: high abundance and sensitivity in rectum and distal colon

¹Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba; ²Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inage-ku, Chiba, Japan; and ³Neuroscience Centre, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Whitechapel, London, United Kingdom

Submitted 5 October 2008 ; accepted in final form 28 May 2009

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.

vanilloid; immunohistochemistry; afferent nerve; substance P; neurokinin A