Improving voiding efficiency in the diabetic rat by a 5-HT1A serotonin receptor agonist
Improving voiding efficiency in the diabetic rat by a 5-HT1A serotonin receptor agonist
复制标题
DOI：
10.1002/nau.21182
复制
发表时间：
2012-01-01
影响因子：
2
通讯作者：
Andersson, Karl-Erik
中科院分区：
文献类型：
--
作者：
Gu, Baojun;Wu, Gang;Andersson, Karl-Erik
5-羟色胺对正常大鼠排尿的影响不仅通过作用于上、下行脊髓通路和脊髓上中枢，还通过作用于腰椎脊髓水平。选择性5-HT1a受体激动剂8-OH-DPAT((R)-(+)-8-hydroxy-2-(di-n-propylamino)，可逆转脊髓损伤(SCI)大鼠逼尿肌-括约肌协同失调。实验性糖尿病(DM)大鼠在反射性排尿过程中出现膀胱和尿路功能障碍。因此，我们研究了8-羟基-DPAT对糖尿病大鼠排尿的影响。方法：选用雌性SD大鼠。以链脲佐菌素(STZ，65 mg/kg)腹腔注射诱导大鼠糖尿病模型，8周后进行膀胱测量。同时测量外括约肌肌电信号(EUS-EMG)。5-HT1a拮抗剂Way-100635(N-叔丁基-3(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide)在每次8-OH-DPAT剂量反应后给药。结果：与对照组相比，DM组大鼠膀胱容量、残存容量增加，排尿效率降低。糖尿病大鼠静脉注射8-羟基-DPAT(3-1000 mg/kg)可剂量依赖性地增加排尿量，减少残余尿量，提高排尿效率。在排尿过程中，随着排尿效率的提高，时相EUS活性呈剂量依赖性增加。Way-100635(300 mg/kg，静脉注射)逆转8-OH-DPAT引起的改变。结论：DM大鼠膀胱排尿效率和周期性EUS活动均降低。5-HT1a受体激动剂可促进周期性EUS活动，从而提高排尿效率。这些结果是否可能对未来排尿的治疗有影响
Aims Serotonin affects micturition in the normal rat through actions not only on ascending and descending spinal pathways and supraspinal centers but also on the lumbosacral spinal cord level. The selective 5-HT1A receptor agonist, 8-OH-DPAT((R)-(+)-8-hydroxy-2-(di-n-propylamino) tetralin), reversed detrusor-sphincter dyssynergia (DSD) in the spinal cord injury (SCI) rat. Rats with experimental diabetes mellitus (DM) have been shown to have both bladder and urethral dysfunction during reflex voiding. We therefore examined the effects of 8-OH-DPAT on micturition in DM rats. Methods: Female Sprague-Dawley rats were used. DM was induced by an intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) and a cystometric study was performed 8 weeks post-injection. External urethral sphincter electromyography (EUS-EMG) was also measured. The 5-HT1A antagonist WAY-100635(N-tert-butyl-3( 4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide) was administered after each 8-OH-DPAT dose-response. Results: Compared to controls, DM rats had a higher bladder capacity, residual volume, and a lower voiding efficiency. In DM rats, 8-OH-DPAT (3-1,000 mg/kg, i. v.) induced significant dose-dependent increases in micturition volume, and decreases in residual volume, resulting in increases in voiding efficiency. During the micturition, there was a dosedependent increased phasic EUS activity correlated with the improved voiding efficiency. WAY-100635 (300 mg/kg, i. v.) reversed the 8-OH-DPAT-induced changes. Conclusions: Both the bladder voiding efficiency and the periodic EUS activity were decreased in DM rats. 5-HT1A receptor agonism promoted periodic EUS activity, thereby improving voiding efficiency. Whether or not these results may have implications for the future treatment of voiding