The Effect of the 5-HT2A/2C Receptor Agonist DOI on Micturition in Rats with Chronic Spinal Cord Injury

被引:21
作者
Chen, Jiasheng
Gu, Baojun
Wu, Gang
Tu, Hongjian
Si, Jieming
Xu, Yuemin
Andersson, Karl-Erik [1 ]
机构
[1] Wake Forest Univ, Bowman Gray Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC USA
基金
中国国家自然科学基金;
关键词
urethra; urinary bladder; spinal cord injuries; lower urinary tract symptoms; serotonin 5-HT2 receptor agonists; EXTERNAL URETHRAL SPHINCTER; LOWER URINARY-TRACT; ANESTHETIZED FEMALE RAT; 2A RECEPTORS; BLADDER; MECHANISMS; 5-HT1A; PHARMACOLOGY; TRANSECTION; DYSFUNCTION;
D O I
10.1016/j.juro.2012.11.049
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: We examined the effects of the 5-HT2A/2C receptor agonist DOI on micturition in chronic spinal cord injured rats. Materials and Methods: Female Sprague-Dawley (R) rats were used. Spinal cord injury was produced by transection at the T10 level. A cystometric study was performed 8 to 12 weeks after transection. Cystometrograms were done using urethane anesthesia in all rats. The selective 5-HT2A antagonist ketanserin was administered after each DOI dose-response curve. All drugs were administered intravenously. Results: Compared to controls, spinal cord injured rats had higher bladder capacity and post-void residual urine volume, and lower voiding efficiency. In spinal cord injured rats DOI (0.01 to 0.3 mg/kg) induced significant dose dependent increases in micturition volume and decreases in residual volume, resulting in increased voiding efficiency. Cystometrogram measurements showed a dose dependent increase in high frequency oscillation activity, evident as an increased number of small oscillation per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI induced changes. Conclusions: High frequency oscillation seems to reflect external urethral sphincter burst activity during voiding. Bladder voiding efficiency and high frequency oscillation activity were decreased in spinal cord injured rats. High frequency oscillation activity can be enhanced by 5-HT2A receptor agonism, improving voiding efficiency. To our knowledge it remains to be studied whether these results may have implications for the future treatment of voiding dysfunction in patients with spinal cord injury.
引用
收藏
页码:1982 / 1988
页数:7
相关论文
共 29 条
[1]   Pharmacology of the lower urinary tract: Basis for current and future treatments of urinary incontinence [J].
Andersson, KE ;
Wein, AJ .
PHARMACOLOGICAL REVIEWS, 2004, 56 (04) :581-631
[2]   Serotonergic drugs and spinal cord transections indicate that different spinal circuits are involved in external urethral sphincter activity in rats [J].
Chang, Hui-Yi ;
Cheng, Chen-Li ;
Chen, Jia-Jin J. ;
de Groat, William C. .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2007, 292 (03) :F1044-F1053
[3]   Effect of a 5-HT1A receptor agonist (8-OH-DPAT) on the external urethral sphincter activity in the rat [J].
Chen, Shih-Ching ;
Fan, Wen-Jia ;
Lai, Chien-Hung ;
Chen, Jia-Jin Jason ;
Peng, Chih-Wei .
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION, 2012, 111 (02) :67-76
[4]   Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury [J].
de Groat, WC ;
Yoshimura, N .
AUTONOMIC DYSFUNCTION AFTER SPINAL CORD INJURY, 2006, 152 :59-84
[5]   Influence of central serotonergic mechanisms on lower urinary tract function [J].
de Groat, WC .
UROLOGY, 2002, 59 (5A) :30-36
[6]   Activation of the external urethral sphincter central pattern generator by a 5-HT1A receptor agonist in rats with chronic spinal cord injury [J].
Dolber, Paul C. ;
Gu, Baojun ;
Zhang, Xiaoyang ;
Fraser, Matthew O. ;
Thor, Karl B. ;
Reiter, Jerome P. .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2007, 292 (04) :R1699-R1706
[7]   The 5-HT2A receptor is widely distributed in the rat spinal cord and mainly localized at the plasma membrane of postsynaptic neurons [J].
Doly, S ;
Madeira, A ;
Fischer, J ;
Brisorgueil, MJ ;
Daval, G ;
Bernard, R ;
Vergé, D ;
Conrath, M .
JOURNAL OF COMPARATIVE NEUROLOGY, 2004, 472 (04) :496-511
[8]   Induction of bladder sphincter dyssynergia by κ-2 opioid receptor agonists in the female rat [J].
Gu, BJ ;
Fraser, MO ;
Thor, KB ;
Dolber, PC .
JOURNAL OF UROLOGY, 2004, 171 (01) :472-477
[9]   MOLECULAR PHARMACOLOGY AND BIOLOGY OF 5-HT1C RECEPTORS [J].
HOYER, D .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1988, 9 (03) :89-94
[10]   Reflex pathways controlling urethral striated and smooth muscle function in the male rat [J].
Kakizaki, H ;
Fraser, MO ;
De, WC .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1997, 272 (05) :R1647-R1656