title: Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder.
abstract: OBJECTIVE
  To investigate the distribution of the transient receptor potential (TRP) A1 ion channel in the rat urinary bladder, and to study the effects of hydrogen sulfide (H(2)S) and known TRPA1 activators on micturition in conscious rats and on heterologously expressed ion channels.
  
  
  METHODS
  The expression of TRPA1 in urinary bladder was studied with fluorescence immunohistochemistry and real-time PCR in female Sprague-Dawley rats. Cystometric investigations were performed in conscious animals subjected to intravesical administration of sodium hydrogen sulfide (NaHS, donor of H(2)S), allyl isothiocyanate (AI), and cinnamaldehyde (CA). Fluorometric calcium imaging was used to study the effect of NaHS on human and mouse TRPA1 expressed in CHO cells.
  
  
  RESULTS
  TRPA1 immunoreactivity was found on unmyelinated nerve fibres within the urothelium, suburothelial space, and muscle layer as well as around blood vessels throughout the bladder. All TRPA1 immunoreactive nerves fibres also expressed TRPV1 immunoreactivity and vice versa. TRPA1 was also detected in urothelial cells at both transcriptional and protein levels. AI increased micturition frequency and reduced voiding volume. CA and NaHS produced similar changes in urodynamic parameters after disruption of the urothelial barrier with protamine sulfate. NaHS also induced calcium responses in TRPA1-expressing CHO cells, but not in untransfected cells.
  
  
  CONCLUSIONS
  The expression of TRPA1 on C-fibre bladder afferents and urothelial cells together with the finding that intravesical TRPA1 activators initiate detrusor overactivity indicate that TRPA1 may have a role in sensory transduction in this organ. The study also highlights H(2)S as a TRPA1 activator potentially involved in inflammatory bladder disease.
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Tomi
authors.initials: T
authors.lastname: Streng
authors.forename: Helena E
authors.initials: HE
authors.lastname: Axelsson
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
authors.forename: David A
authors.initials: DA
authors.lastname: Andersson
authors.forename: Sven-Eric
authors.initials: SE
authors.lastname: Jordt
authors.forename: Stuart
authors.initials: S
authors.lastname: Bevan
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Edward D
authors.initials: ED
authors.lastname: Högestätt
authors.forename: Peter M
authors.initials: PM
authors.lastname: Zygmunt
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000344:Afferent Pathways; D000704:Analysis of Variance; D000818:Animals; D017487:Ankyrins; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006862:Hydrogen Sulfide / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D017879:Isothiocyanates / Q000494:pharmacology; D018613:Microscopy, Confocal; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D001743:Urinary Bladder / Q000294:innervation* / Q000378:metabolism / Q000502:physiology; D014554:Urination / Q000187:drug effects
chemical_list: D017487:Ankyrins; D015220:Calcium Channels; D007473:Ion Channels; D017879:Isothiocyanates; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D000171:Acrolein; C004471:allyl isothiocyanate; C012843:cinnamaldehyde; D006862:Hydrogen Sulfide