title: Individual receptor profiling as a novel tool to support diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC).
abstract: OBJECTIVE
  Dysregulation of neurotransmitter receptors may contribute to bladder overactivity (OAB) symptoms. To address the question whether specific receptor expression patterns are associated with bladder pain syndrome/interstitial cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and histamine receptors in the detrusor.
  
  
  METHODS
  Detrusor receptor expression was investigated in bladder biopsies of female BPS/IC patients (n = 44; age 60.64 ± 13.78, mean ± SD) and carcinoma patients (n = 11; age 58.91 ± 12.72) undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic (P2X1-3) and histamine receptors (H1, H2) was analysed by confocal immunofluorescence, and gene expression was quantified by real-time polymerase chain reaction (qPCR).
  
  
  RESULTS
  M2, P2X1, P2X2 and H1 receptor immunoreactivity (-IR) was significantly enhanced in BPS/IC compared to the control group, while there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09% sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated risk for BPS/IC. In addition, two patient subgroups (M2 > M3 and M3 > M2) were observed, which differed in associated purinergic and histamine receptor expression.
  
  
  CONCLUSIONS
  M2, P2X1, P2X2 and H1 were significantly upregulated in BPS/IC patients, and H2 was occasionally highly overexpressed. There was no significant correlation between receptor protein and gene expression, implying posttranslational mechanisms being responsible for the altered receptor expressions. On the basis of individual receptor profiles, upregulated receptors could be targeted by monotherapy or combination therapy with already approved receptor inhibitors, thereby promoting tailored therapy for patients suffering from BPS/IC-like symptoms.
authors.affiliation: Department of Urology, University Hospital Leipzig, Liebigstr. 20, 04103 Leipzig, Germany. jochen.neuhaus@medizin.uni-leipzig.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Neuhaus
authors.forename: Heinrich
authors.initials: H
authors.lastname: Schulte-Baukloh
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Stolzenburg
authors.forename: Pietro
authors.initials: P
authors.lastname: Speroni di Fenizio
authors.forename: Lars-Christian
authors.initials: LC
authors.lastname: Horn
authors.forename: Henrik
authors.initials: H
authors.lastname: Rüffert
authors.forename: Siegurd
authors.initials: S
authors.lastname: Hartenstein
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.forename: Matthias
authors.initials: M
authors.lastname: Schulze
authors.forename: Thilo
authors.initials: T
authors.lastname: Schwalenberg
mesh_terms: D000368:Aged; D001706:Biopsy; D018856:Cystitis, Interstitial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D043585:Receptor, Muscarinic M2 / Q000235:genetics / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000235:genetics / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism; D058474:Receptors, Purinergic P2X1 / Q000235:genetics / Q000378:metabolism; D058476:Receptors, Purinergic P2X2 / Q000235:genetics / Q000378:metabolism; D058477:Receptors, Purinergic P2X3 / Q000235:genetics / Q000378:metabolism; D013577:Syndrome; D059467:Transcriptome; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism
chemical_list: D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D058474:Receptors, Purinergic P2X1; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3