Role of α2-Adrenoceptors and Glutamate Mechanisms in the External Urethral Sphincter Continence Reflex in Rats
Role of α2-Adrenoceptors and Glutamate Mechanisms in the External Urethral Sphincter Continence Reflex in Rats
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DOI：
10.1016/j.juro.2008.11.008
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发表时间：
2009-03-01
影响因子：
6.6
通讯作者：
Yoshimura, Naoki
中科院分区：
文献类型：
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作者：
Furuta, Akira;Asano, Koji;Yoshimura, Naoki
目的：我们研究了α（2）-肾上腺素能受体和谷氨酸机制在尿道反射中的作用，在响应腹压increases.Materials和方法：在乌拉坦麻醉下，在脊髓横断（T8-T9）的雌性大鼠在下腹壁压缩之前和之后，静脉内应用测试drugs. Materials和Methods的外尿道括约肌肌电图活动进行了评价。检查N-甲基-D-天冬氨酸谷氨酸受体拮抗剂MK-801（Sigma（R））或α（2）-肾上腺素受体激动剂美托咪定（Tocris Cookson，Ellisville，密苏里州）（静脉注射0.03、0.3和3 mg/kg）对外尿道括约肌活性的影响。然后在静脉内应用1 mg/kg MK-801之前或之后，静脉内给予0.3 mg/kg剂量的α（2）-肾上腺素受体拮抗剂咪唑克生（Sigma）。此外，0.3 mg/kg咪唑克生静脉注射后，应用1 mg/kg的5-羟色胺/去甲肾上腺素再摄取抑制剂度洛沙汀（Kemprotec，Middlesbrough，United Kingdom）intravenous.Results：MK-801和美托咪定剂量依赖性地降低外尿道括约肌活动。咪唑克生使尿道外括约肌活动显著增加64%，但咪唑克生后的活动增加被MK-801消除。另一方面，咪唑克生不能逆转MK-801的抑制作用。此外，咪唑克生可显著增强度洛沙酮对尿道外括约肌活性的作用，增幅达120%。这些结果表明：1）谷氨酸是腹压增加引起的尿道反射反应中的主要兴奋性神经递质，2）α（2）-肾上腺素受体激活抑制尿道外括约肌活动，可能通过突触前抑制谷氨酸释放和3）5-羟色胺/去甲肾上腺素再摄取抑制剂的作用通过α（2）-肾上腺素受体抑制而增强。因此，α（2）-肾上腺素受体拮抗剂可能是有益的治疗压力性尿失禁。
Purpose: We investigated the role of alpha(2)-adrenoceptors and glutamate mechanisms in the urethral continence reflex in response to abdominal pressure increases.Materials and Methods: Under urethane anesthesia external urethral sphincter electromyogram activity was evaluated in spinal cord transected (T8-T9) female rats during lower abdominal wall compression before and after intravenous application of test drugs. The effects of the N-methyl-D-aspartate glutamate receptor antagonist MK-801 (Sigma (R)) or the alpha(2)-adrenoceptor agonist medetomidine (Tocris Cookson, Ellisville, Missouri) (each 0.03, 0.3 and 3 mg/kg intravenously) on external urethral sphincter activity were examined. A 0.3 mg/kg intravenous dose of the alpha(2)-adrenoceptor antagonist idazoxan (Sigma) was then administered before or after the application of 1 mg/kg MK-801 intravenously. In addition, 0.3 mg/kg idazoxan were administered intravenously following the application of 1 mg/kg of the serotonin/norepinephrine reuptake inhibitor duloxetine (Kemprotec, Middlesbrough, United Kingdom) intravenously.Results: MK-801 and medetomidine dose dependently decreased external urethral sphincter activity. Idazoxan significantly increased external urethral sphincter activity by 64% but the increase in activity after idazoxan was abolished by MK-801. On the other hand, idazoxan did not reverse the inhibitory effects of MK-801. In addition, idazoxan significantly potentiated the duloxetine effects on external urethral sphincter activity by 120%.Conclusions: These results indicate that 1) glutamate is a major excitatory neurotransmitter in the urethral continence reflex response to abdominal pressure increases, 2) alpha(2)-adrenoceptor activation suppresses external urethral sphincter activity, probably via presynaptic inhibition of glutamate release and 3) the effects of serotonin/norepinephrine reuptake inhibitors are enhanced by alpha(2)-adrenoceptor inhibition. Therefore, alpha(2)-adrenoceptor antagonists could be beneficial for treating stress urinary incontinence.