Transient receptor potential channel A1 involved in sensory transduction of rat urinary bladder through C-fiber pathway

OBJECTIVES To investigate the expression and function of the transient receptor potential (TRP) channel A1 in the afferent pathway of rat urinary bladder. The TRPA1 is a candidate for both mechanosensory transduction and nociception. METHODS Quantitative reverse transcriptase-polymerase chain reaction and immunofluorescent staining was used to investigate the expression of TRPA1 in primary sensory neurons innervating the rat bladder. Cystometry was performed by intravesically infusing agonists of TRPA1 (trans-cinnamaldehyde or allyl isothiocyanate) in normal and capsaicin-pretreated urethane-anesthetized rats. RESULTS TRPA1 mRNA was expressed in L6-S1 dorsal root ganglia (DRG) and bladder. The expression level for DRG/bladder mucosa/bladder muscular layer was 199:16:1. Its immunoreactivity was found in the small neurons of L6-S1 DRG. Of the bladder-innervating DRG neurons identified by retrograde labeling, 50.8% showed TRPAl immunoreactivity. TRPA1 and calcitonin-gene related peptide were co-localized in subepithelial sensory nerves of the bladder. Intravesical perfusion of 600 mu M trans-cinnamaldehyde significantly decreased the intercontraction interval and pressure threshold to 59.8% and 83.8% of their control value, respectively. The effects of trans-cinnamaldehyde were reversible by washing out the drug. Desensitization of C-fibers by capsaicin markedly attenuated the transcinnamaldehyde effects. Also, 400 mu M allyl isothiocyanate reversibly and significantly decreased the intercontraction interval to 64.7% of its control value. CONCLUSIONS TRPA1 is expressed in the bladder-innervating primary sensory neurons. Its agonists cause bladder hyperreflexia through C-fiber-mediated afferent pathway. TRPA1 might be involved in the bladder afferent transduction as a mechanotransducer and/or nociceptor.