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The effect of the 5‐HT7 serotonin receptor agonist, LP44, on micturition in rats with chronic spinal cord injury
Author(s) -
Gang Wu,
Hongjian Tu,
Jasheng Chen,
Jiemin Si,
Zhong Chen,
Yuemin Xu,
Baojun Gu,
Andersson KarlErik
Publication year - 2014
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.22463
Subject(s) - urination , medicine , agonist , spinal cord injury , anesthesia , 5 ht receptor , overactive bladder , serotonin , spinal cord , receptor , urology , urinary system , alternative medicine , pathology , psychiatry
Aims 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 T 10 level; cystometric study occurred 8–12 weeks post‐transection. Intravesical pressure was monitored in urethane‐anesthetized animals via a transvesical catheter. The selective 5‐HT 7 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‐HT 7 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. Neurourol. Urodynam. 33:1165–1170, 2014 . © 2013 Wiley Periodicals, Inc.