TRPA1 is a Ca2+-permeable cation channel that is activated by painful low
temperatures (˂17 °C), irritating chemicals, reactive metabolites and mediators of
inflammation. In the bladder TRPA1 is predominantly expressed in sensory afferent nerve
endings, where it mediates sensory transduction. The contractile effect of its activation
on detrusor smooth muscle (DSM) is explained by the release from sensory afferents of
inflammatory factors – tachykinins and prostaglandins, which cause smooth muscle cell
contraction. Diabetes is a systemic disease, with common complications being diabetic
cystopathies and urinary incontinence. However, data on how diabetes affects bladder
contractility associated with TRPA1 activation are not available. In this study, by using
a rat model with streptozotocin-induced type I diabetes, contractility measurements of DSM
strips in response to TRPA1-activating and modulating pharmacological agents and
assessment of TRPA1 mRNA expression in bladder-innervating dorsal root ganglia, we have
shown that diabetes enhances the TRPA1-dependent mechanism involved in bladder DSM
contractility. This is not due to changes in TRPA1 expression, but mainly due to the
general inflammatory reaction caused by diabetes. The latter leads to an increase in
cyclooxygenase-2-dependent prostaglandin synthesis through the mechanisms associated with
substance P activity. This results in the enhanced functional coupling between the
tachykinin and prostanoid systems, and the concomitant increase of their impact on DSM
contractility in response to TRPA1 activation.
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