title: Immunolocalization of multidrug resistance protein 5 in the human genitourinary system.
abstract: OBJECTIVE
  The intracellular messenger cyclic guanosine monophosphate (cGMP) has an important role in regulating smooth muscle tone. An increase in intracellular cGMP levels is a prerequisite for penile erection. Inhibition of cGMP degradation by cGMP specific phosphodiesterase 5 has been used for treating erectile dysfunction. In addition to degradation by phosphodiesterase, cGMP is exported from cells by multidrug resistance protein 5 (MRP5), also called ABCC5, which we recently identified as an adenosine triphosphate dependent export pump for cGMP. MRP5 is potently inhibited by substances known as phosphodiesterase inhibitors, including sildenafil and trequinsin. Therefore, we analyzed whether MRP5 is expressed in tissues of the human genitourinary system and whether MRP5 and phosphodiesterase 5 proteins are localized in the same cell types.
  
  
  METHODS
  Localization of MRP5 and phosphodiesterase 5 was analyzed by immunofluorescence microscopy in cryosections of various tissues of the human genitourinary system.
  
  
  RESULTS
  MRP5 and phosphodiesterase 5 were co-expressed in smooth muscle cells of the corpus cavernosum, ureter, urethra and bladder. In addition, MRP5 and phosphodiesterase 5 were localized in epithelial cells of the mucosa in the ureter and urethra, and in blood vessels of the lamina propria.
  
  
  CONCLUSIONS
  The co-expression of MRP5 and phosphodiesterase 5 in smooth muscle cells of the genitourinary system indicates 2 distinct pathways for cGMP removal. Thus, MRP5 inhibition represents a new approach for enhancing cGMP levels in smooth muscle cells and developing drugs for erectile dysfunction.
authors.affiliation: Divisions of Tumor Biochemistry and Cell Biology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Nies
authors.forename: Herbert
authors.initials: H
authors.lastname: Spring
authors.forename: Walter F
authors.initials: WF
authors.lastname: Thon
authors.forename: Dietrich
authors.initials: D
authors.lastname: Keppler
authors.forename: Gabriele
authors.initials: G
authors.lastname: Jedlitschky
mesh_terms: D000328:Adult; D000368:Aged; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis*; D009130:Muscle, Smooth / Q000033:anatomy & histology; D010410:Penile Erection / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014566:Urogenital System / Q000033:anatomy & histology*
chemical_list: D000242:Cyclic AMP; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C120809:ABCC5 protein, human