title: TRPA1-dependent regulation of bladder detrusor smooth muscle contractility in normal and type I diabetic rats.
abstract: TRPA1 is a Ca(2+)-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.
authors.affiliation: Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Philyppov
authors.forename: Oksana N
authors.initials: ON
authors.lastname: Paduraru
authors.forename: Kseniya L
authors.initials: KL
authors.lastname: Gulak
authors.forename: Roman
authors.initials: R
authors.lastname: Skryma
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
authors.forename: Yaroslav M
authors.initials: YM
authors.lastname: Shuba
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000235:genetics* / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology*; D011453:Prostaglandins / Q000096:biosynthesis; D017208:Rats, Wistar; D013311:Streptozocin; D013373:Substance P / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism; D001743:Urinary Bladder / Q000503:physiopathology*
chemical_list: D011453:Prostaglandins; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; D013373:Substance P; D013311:Streptozocin; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat