title: The effect of the 5-HT7 serotonin receptor agonist, LP44, on micturition in rats with chronic spinal cord injury.
abstract: OBJECTIVE
  To better understand the effects of the selective 5-HT7 receptor agonist 4-[2-(Methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-piperazinehexanamide hydrochloride (LP44) on micturition in spinal cord injury (SCI) rats.
  
  
  METHODS
  Female Sprague-Dawley rats weighing 200-275 g were used. SCI was produced in 8 of the 16 rats by transection at the T10 level; cystometric study occurred 8-12 weeks post-transection. Intravesical pressure was monitored in urethane-anesthetized animals via a transvesical catheter. The selective 5-HT7 antagonist (R)-3-[2-[2-(4-Methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl] phenol hydrochloride (SB-269970) was administered after each LP44 dose-response curve (all drugs were administered intravenously, i.v).
  
  
  RESULTS
  Compared to controls, SCI rats had a higher bladder capacity and residual volume, and a lower voiding efficiency. In SCI rats, LP44 (0.003-0.3 mg/kg, i.v) induced significant dose-dependent increases in micturition volume, significant dose-dependent decreases in residual volume, resulting in significant increases in voiding efficiency. CMG measurements showed a dose-dependent increase of the high-frequency oscillation (HFO) activity, including the number of small oscillation per voiding. This was correlated with the improved voiding efficiency. SB-269970 (0.1 mg/kg, i.v) partially or completely reversed all LP44-induced changes.
  
  
  CONCLUSIONS
  HFOs seems to be correlated with external urethral sphincter (EUS) bursting activity during voiding. Both the bladder voiding efficiency and the periodic EUS activity were decreased in SCI rats. 5-HT7 receptor agonist can enhance HFO activity, thereby improving voiding efficiency. Whether or not these results may have implications for the future treatment of voiding dysfunction in SCI patients remains to be studied.
authors.affiliation: Department of Urology, Shanghai 6th People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Gang
authors.forename: Tu
authors.initials: T
authors.lastname: Hongjian
authors.forename: Chen
authors.initials: C
authors.lastname: Jasheng
authors.forename: Si
authors.initials: S
authors.lastname: Jiemin
authors.forename: Chen
authors.initials: C
authors.lastname: Zhong
authors.forename: Xu
authors.initials: X
authors.lastname: Yuemin
authors.forename: Gu
authors.initials: G
authors.lastname: Baojun
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000818:Animals; D004576:Electromyography; D005260:Female; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D014554:Urination / Q000187:drug effects*; D014555:Urination Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: C495230:4-(2-methylthiophenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013764:Tetrahydronaphthalenes; C104425:serotonin 7 receptor
keywords: 5-HT7 receptors; external urethral sphincter; micturition; spinal cord injury