title: Functional and molecular characterization of hyposensitive underactive bladder tissue and urine in streptozotocin-induced diabetic rat.
abstract: BACKGROUND
  The functional and molecular alterations of nerve growth factor (NGF) and Prostaglandin E2 (PGE2) and its receptors were studied in bladder and urine in streptozotocin (STZ)-induced diabetic rats.
  
  
  RESULTS
  Diabetes mellitus was induced with a single dose of 45 mg/kg STZ Intraperitoneally (i.p) in female Sprague-Dawley rats. Continuous cystometrogram were performed on control rats and STZ treated rats at week 4 or 12 under urethane anesthesia. Bladder was then harvested for histology, expression of EP receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all groups for urine levels of PGE2, and NGF assay. DM induced progressive increase of bladder weight, urine production, intercontraction interval (ICI) and residual urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP)1 and EP3 receptors and downregulation of NGF expression, increase in urine NGF and decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM group at week 12.
  
  
  CONCLUSIONS
  DM induced hyposensitive underactive bladder which is characterized by increased inflammatory reaction, apoptosis, urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF and urine PGE2. The data suggest that EP3 receptor are potential targets in the treatment of diabetes induced underactive bladder.
authors: Department of Urology, Centre for Urology Research Excellence, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors: Jayabalan
authors: J
authors: Nirmal
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Pradeep
authors: P
authors: Tyagi
authors: Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Yao-Chi
authors: YC
authors: Chuang
authors: Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Wei-Chia
authors: WC
authors: Lee
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Naoki
authors: N
authors: Yoshimura
authors: Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Chao-Cheng
authors: CC
authors: Huang
authors: Department of Urology, Centre for Urology Research Excellence, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors: Bharathi
authors: B
authors: Rajaganapathy
authors: Department of Urology, Centre for Urology Research Excellence, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors: Michael B
authors: MB
authors: Chancellor
mesh_terms: D000818:Animals; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000652:urine; D015232:Dinoprostone / Q000652:urine; D005260:Female; D020932:Nerve Growth Factor / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism; D013311:Streptozocin; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001745:Urinary Bladder Diseases / Q000209:etiology / Q000503:physiopathology* / Q000652:urine
chemical_list: D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D013311:Streptozocin; D020932:Nerve Growth Factor; D015232:Dinoprostone