title: Transient receptor potential A1 (TRPA1) activity in the human urethra--evidence for a functional role for TRPA1 in the outflow region.
abstract: BACKGROUND
  A role for the transient receptor potential (TRP) A1 ion channel in rat lower urinary tract (LUT) sensation and disease has been proposed, but in the human LUT no information on TRPA1 activity is available.
  
  
  OBJECTIVE
  To investigate the distribution of TRPA1 in the human urethra and to study the effect of TRPA1 agonists on isolated urethral strip preparations.
  
  
  METHODS
  Urethral specimens were obtained preoperatively from 10 patients and were freshly prepared for Western blot, immunohistochemistry, and functional in vitro investigations.
  
  
  METHODS
  The expression patterns of TRPA1 were studied with Western blot and immunohistochemistry. The effects of allyl isothiocyanate (AI), cinnamaldehyde (CA), and NaHS (donor of H(2)S) on tension of urethral strips were investigated in tissue baths.
  
  
  CONCLUSIONS
  TRPA1 immunoreactivity (-IR) was found in nerve fibres in the suburothelial space and was also located to nerve fibres of the muscle layer. Single TRPA1-IR nerves extended into the urothelium. A majority, but not all TRPA1-IR nerves also expressed immunoreactivity for CGRP or TRPV1. In the urothelium, TRPV1 was located to the outer layers whereas TRPA1 was observed in basal urothelial cells. Interspersed between strands of smooth muscle cells of the urethral wall, TRPA1- and vimentin-IR cells containing central nuclei and slender cytoplasmatic extensions were observed. In functional experiments, TRPA1-agonists had no contractile effect in urethral preparations. After precontraction with phenylephrine, AI, CA, and NaHS caused concentration-dependent relaxations of urethral strip preparations.
  
  
  CONCLUSIONS
  The localization of TRPA1 to nerves that also express TRPV1 and CGRP, and in urothelial cells and interstitial cells, as well as the findings that TRPA1 agonists can modify tone of urethral preparations, propose a role for TRPA1 in afferent and efferent sensory signaling of the human outflow region.
authors.affiliation: Department of Clinical Chemistry and Pharmacology, Lund University Hospital, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Gratzke
authors.forename: Tomi
authors.initials: T
authors.lastname: Streng
authors.forename: Eginhard
authors.initials: E
authors.lastname: Waldkirch
authors.forename: Katja
authors.initials: K
authors.lastname: Sigl
authors.forename: Christian
authors.initials: C
authors.lastname: Stief
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018689:Sensory System Agents / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D014521:Urethra / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D017879:Isothiocyanates; D018689:Sensory System Agents; D013440:Sulfides; D050052:TRPC Cation Channels; D000171:Acrolein; C004471:allyl isothiocyanate; C025451:sodium bisulfide; D002211:Capsaicin; C012843:cinnamaldehyde