title: Changes in alpha1-adrenoceptor and NGF/proNGF pathway: a possible mechanism in diabetic urethral dysfunction.
abstract: OBJECTIVE
  To investigate the changes in the α1-adrenoceptor and nerve growth factor (NGF)/NGF precursor (proNGF) pathway in the urethra after diabetes induction.
  
  
  METHODS
  Urethral relaxation function was determined by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) in diabetic rats. The expression of α1-adrenoceptor, NGF, proNGF, low-affinity p75 receptor for neurotrophins (p75(NTR)) and sortilin in the urethras was measured using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay and Western blotting.
  
  
  RESULTS
  In diabetic rats, the lowest urethral pressure (UPP nadir) during urethral relaxation was significantly higher. Intravenous administration of tamsulosin, an α1-adrenoceptor antagonist, significantly decreased the UPP nadir and baseline UPP in diabetic rats. RT-qPCR and Western blotting studies showed a statistically significant increase of α1a- and α1b-adrenoceptor in the urethras from the diabetic group (p < 0.05). The expression of NGF was significantly decreased in the urethras from the diabetic group while the expression of proNGF was significantly increased (p < 0.05). The p75(NTR) level in the urethras of diabetic rats was decreased compared with controls (p < 0.05) and there was no significant difference regarding sortilin between the two groups (p > 0.05).
  
  
  CONCLUSIONS
  This study validated the diabetic urethral dysfunction and furthermore indicated that the increase in the expression of α1-adrenoceptor and changes in the NGF/proNGF pathway may be involved in diabetic urethral dysfunction.
authors.affiliation: Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Shouzhen
authors.initials: S
authors.lastname: Chen
authors.forename: Yaofeng
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Feng
authors.forename: Zhaocun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shun
authors.initials: S
authors.lastname: Li
authors.forename: Benkang
authors.initials: B
authors.lastname: Shi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage; D000818:Animals; D048909:Diabetes Complications; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020932:Nerve Growth Factor / Q000378:metabolism*; D010477:Perfusion; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013449:Sulfonamides / Q000008:administration & dosage; D000077409:Tamsulosin; D014521:Urethra / Q000503:physiopathology*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D058668:Adrenergic alpha-1 Receptor Antagonists; D020932:Nerve Growth Factor; D020800:Receptor, Nerve Growth Factor; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D000077409:Tamsulosin; D000099183:Sortilin