Reversible changes in bladder urothelial permeability at low temperatures are mediated by TRPA1

It has been suggested that physical or chemical stimuli may alter the permeability of the bladder urothelium. This study explored factors that could reversibly alter the urothelial permeability in the rat bladder and evaluated their mechanisms. Female Sprague–Dawley rats were used. An organ bath study using inside-out bladder preparations was performed to assess changes in urothelial permeability induced by low temperature and transient receptor potential ankyrin 1 (TRPA1) activation. The Ussing chamber study using urothelium–lamina propria sheets was performed to assess changes in transepithelial electrical resistance (TEER). In those studies, KCl, acetylcholine (ACh), allyl isothiocyanate (AITC), a TRPA1 agonist, and HC-030031, a TRPA1 antagonist, were applied to the urothelial side. In inside-out preparations, KCl induced slight bladder contraction at 37 °C, whereas marked contractions were observed at 17 °C and 7 °C. These responses disappeared after rewarming to 37 °C. The response at 17 °C was attenuated by HC-030031 in a concentration-dependent manner. At 37 °C, pretreatment with AITC facilitated KCl-induced contractions. In Ussing chamber studies at 37 °C, application of AITC to the urothelial side gradually decreased TEER, indicating increased bladder urothelial permeability. This TEER reduction was attenuated by HC-030031. These results suggest that low temperature and TRPA1 activation reversibly enhance bladder urothelial permeability.