title: Serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) improves voiding efficiency in the diabetic rat.
abstract: OBJECTIVE
  To examine the effects of the serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) on micturition in rats with diabetes mellitus (DM).
  
  
  METHODS
  Female Sprague-Dawley rats (n = 16) were divided into two groups: rats with Type 1 DM and age-matched control rats. DM was induced by i.p. injection of streptozotocin (65 mg/kg) and detailed cystometrogram (CMG) studies were performed 8 weeks post-injection in all rats under urethane anaesthesia. The selective 5-HT2A antagonist ketanserin was administered after each DOI dose-response curve was plotted. All drugs were administered i.v.
  
  
  RESULTS
  Compared with controls, comprehensive urodynamic studies showed that DM rats had a higher bladder capacity and post-void residual urine volume (PVR), and a markedly lower voiding efficiency. In DM rats, DOI (0.01-0.3 mg/kg) induced significant dose-dependent increases in micturition volume and reductions in PVR, resulting in greater voiding efficiency. CMG measurements showed a dose-dependent increase in high-frequency oscillation (HFO) activity, evidenced by an increased duration of HFOs per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI-induced changes.
  
  
  CONCLUSIONS
  The HFOs observed in the present study seem to correlate with external urethral sphincter bursting activity during voiding. Bladder voiding efficiency was reduced in DM rats. The 5-HT2A receptor agonist can enhance HFO activity and improves voiding efficiency, and so may represent a new strategy to improve voiding efficiency after DM in experimental studies.
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, Jiangsu Province, China.|School of Medicine, Soochow University, Suzhou City, Jiangsu Province, China.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Tu
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, Jiangsu Province, China.
authors.forename: Nailong
authors.initials: N
authors.lastname: Cao
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, Jiangsu Province, China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Gu
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, Jiangsu Province, China.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Si
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, Jiangsu Province, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA.
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D014554:Urination / Q000187:drug effects*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists
keywords: 5-HT2A receptor agonist; diabetic rat; external urethral sphincter; micturition