title: Does bladder outlet obstruction alter the non-neuronal cholinergic system of the human urothelium?
abstract: OBJECTIVE
  Alterations of the bladder sensory system are considered to contribute to detrusor overactivity (DO) when patients suffer from bladder outlet obstruction (BOO). The urothelium is one part of this sensory system and it harbors a non-neuronal cholinergic system (NNCS). We aimed to investigate if BOO causes alterations in the NNCS.
  
  
  METHODS
  Urothelial specimens were collected by endoscopy from six male controls and eight male patients suffering from BOO and DO. The samples were examined by immunofluorescence (IF) and real-time RT-PCR for high-affinity choline transporter-1 (CHT1), choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), organic cation transporters OCT1-3, muscarinic receptor (mAChR) subtypes M1-M5 and nicotinic receptor (nAChR) subunits α7, α9 and α10.
  
  
  RESULTS
  ChAT, VAChT and OCT2 are not present in the male urothelium. Real-time RT-PCR and IF detected all other investigated targets. Rank order of expression was M2≫M3=M5>M4=M1 for mAChR subtypes and α7≫α10>α9 for nAChR subunits. Statistical analysis of RT-PCR results did not detect significant differences between patients and controls. Only IF detected differences between both groups: α9-Immunolabeling was increased in all BOO/DO patients.
  
  
  CONCLUSIONS
  BOO does not induce considerable alterations of the human urothelial NNCS on mRNA level. Expression of mAChRs, CHT1, OCT1 and OCT3 is not significantly affected by BOO. Thus, transport mechanisms for choline and acetylcholine (ACh) stay unaltered. BOO increases immunolabeling of α9-nAChR but whether this sole finding contributes to the onset of DO seems questionable. Comparing the present results with our previous work, the urothelial NNCS does not differ between men and women.
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Justus-Liebig-University, UKGM, Rudolf-Buchheim-Strasse 7, 35392 Giessen, Germany. Th.B@gmx.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Bschleipfer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weidner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
authors.forename: Katrin S
authors.initials: KS
authors.lastname: Lips
mesh_terms: D000368:Aged; D002795:Choline O-Acetyltransferase / Q000032:analysis* / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000032:analysis* / Q000235:genetics; D012313:RNA / Q000235:genetics; D011950:Receptors, Cholinergic / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000032:analysis* / Q000235:genetics; D001748:Urinary Bladder Neck Obstruction / Q000235:genetics / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology*; D050494:Vesicular Acetylcholine Transport Proteins / Q000032:analysis* / Q000235:genetics
chemical_list: D027701:Organic Cation Transport Proteins; D011950:Receptors, Cholinergic; C510731:SLC5A7 protein, human; D027981:Symporters; D050494:Vesicular Acetylcholine Transport Proteins; D012313:RNA; D002795:Choline O-Acetyltransferase