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

Abstract

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.

Impaired colonic motility and reduction in tachykinin signalling in the aged mouse

“…Tachykininsregulate colonic motility via NK 1 and NK 2 receptors. NK 2 receptors are predominantly located on longitudinal and circular smooth muscle cellsin both mice Matsumoto et al, 2009) and humans (Giuliani et al, 1991;Jaafari et al, 2007)and provide the main receptor through which electrical field stimulation (EFS)-evoked release of tachykinins causes smooth muscle contraction. In human colons, application of NK 2 receptor agonists induced contractions,while selective NK 2 antagonists were capable of almost completely blocking EFS-evoked colonic contractions (Giuliani et al, 1991;Nakamura et al, 2011).…”

Vanilloid Receptor-1 Regulates Neurogenic Inflammation in Colon and Protects Mice from Colon Cancer

“…1, 2). In the gastrointestinal tract, TRPV-1 is preferentially expressed in the distal colon (3). TRPV-1 is a molecular integrator of multiple noxious stimuli and a regulator of the body temperature (4).…”

[6]-Gingerol Induces Electrogenic Sodium Absorption in the Rat Colon via the Capsaicin Receptor TRPV1

“…TRPV1 is mainly localized to the nerve fibers in the basolateral side of the mucosa and submucosa in the rat colon, (23) and in the mouse colon (24). TRPV1 has also been detected in nerve fibers of the muscle layer (24). The intestinal sacs used in this study contained the mucosal, submucosal, and muscle layers.…”

“…It has been well established that [6]-gingerol is an agonist of TRPV1. TRPV1 is mainly localized to the nerve fibers in the basolateral side of the mucosa and submucosa in the rat colon, (23) and in the mouse colon (24). TRPV1 has also been detected in nerve fibers of the muscle layer (24).…”