Assessment of Mucosal Movement in the Gastroesophageal Junction High-Pressure Zone During Swallowing Using Simultaneous Endoluminal Ultrasound and Manometry

Abstract

BACKGROUND & AIM: Allyl isothiocyanate, the pungent ingredient of wasabi and mustard oil, is known to activate transient receptor potential (TRP) cation channels TRPA1. TRPA1 was recently shown to be functionally expressed in the gastrointestinal tract, whose ion channel presents in a subpopulation of primary sensory neurons that coexpressed with TRPV1. Previously, we also reported (1) that TRPV1-expressing sensory nerve fivers abundantly exist around blood vessels in the submucosa in the rat stomach, suggesting that TRPV1 plays an important role in control of local blood flow (Scand J. Gastroenterol. 39, 303-312, 2004), and (2) that allyl isothiocyanate facilitates to increase gastric mucosal blood flow (GMBF) in the rat stomach (Gastroenterology 138 (Suppl.1) S-721, 2010). However, the mechanism for the increased GMBF in response to allyl isothiocyanate remains unknown. In the present studies, we examined the effect of a TRPA1 activator allyl isothiocyanate on GMBF in the ex-vivo stomach of normal and sensory deafferented rats. METHODS: Male SD rats (160-200 g) were used after 18 hr-fasting. GMBFwasmeasured in the ex-vivo stomach of urethane-anesthetized rats by using the laser Doppler flowmeter. Allyl isothiocyanate (0.3310 mM) or a TRPV1 channel activator capsaicin (3.3 mM) was topically applied for 10 min to the rat stomach, and changes in GMBF were monitored. Either a TRPA1 channel blocker HC-030031 (14.1 mM) or a TRPV1 channel blocker BCTC (0.8 mM) was co-applied with allyl isothiocyanate (10 mM) for 10 min to the stomach. RESULTS: Mucosal application of allyl isothiocyanate increased GMBF in a concentration-dependentmanner.When themucosa was exposed to allyl isothiocyanate (10 mM) repeatedly, this response showed a marked desensitization. The increased GMBF response caused by allyl isothiocyanate was entirely blocked by co-application with HC-030031, but not BCTC. Interestingly, the increased GMBF in response to allyl isothiocyanate was significantly attenuated, but not completely disappear, by chemical deafferentation following systemic capsaicin injections (total dose: 100 mg/kg), although the increased GMBF in response to capsaicin was completely abolished by chemical deafferentation. The increased GMBF response to capsaicin was also significantly decreased in allyl isothiocyanate-desensitized preparation of the ex-vivo stomach. CONCLUSION: These results suggested that allyl isothiocyanate increases GMBF through activation of TRPA1, but not TRPV1. It is assumed that the increased GMBF in response to allyl isothiocyanate is mediated by TRPA1 located on both TRPV1-expresseing and TRPV1 nonexpressing sensory nerves.