Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder.
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.
Streng
Tomi
T
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Axelsson
Helena E
HE
Hedlund
Petter
P
Andersson
David A
DA
Jordt
Sven-Eric
SE
Bevan
Stuart
S
Andersson
Karl-Erik
KE
Högestätt
Edward D
ED
Zygmunt
Peter M
PM
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
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