Dopaminergic mechanisms controlling urethral function in rats
Dopaminergic mechanisms controlling urethral function in rats
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DOI：
10.1002/nau.20260
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发表时间：
2006-01-01
影响因子：
2
通讯作者：
Yoshimura, Naoki
中科院分区：
文献类型：
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作者：
Ogawa, Teruyuki;Seki, Satoshi;Yoshimura, Naoki
目的：探讨多巴胺受体亚型在控制尿路活动中的作用。方法：乌拉坦麻醉下，同步记录大鼠膀胱内和尿路灌流压(UPP)。静脉注射(Iv)、鞘内注射(I.T.)或脑室注射(i.c.v)后，检查膀胱和尿道括约肌协调活动的变化。给予多巴胺D_1和D_2样受体激动剂(分别为SKF38393和奎比罗)和拮抗剂(分别为SCH23390和RemoxiPride)。结果：昆匹罗0.03、0.1、0.3 mg/kg静脉注射。与对照组(46.0+/-4.0 cm H2O)相比，剂量依赖性地将基础尿压分别降低至45.33+/-5.8、33.7+/-3.3(P<；0.05，n=6)和27.7+/-3.3 cm H2O(P<；0.05，n=5)。I.C.V.注射喹比罗(1 Mg)后，基线尿压从对照组(51.4+/-4.9 cm H2O)降至33.6+/-5.0 cm H2O(P<；0.05，n=4)，而I.T.的作用不显著。给药(3微克)。奎比罗(0.1 mg/kg)静脉注射可降低基线血压。被神经肌肉阻滞剂α-银环蛇毒素(BGT)抑制。SCH23390(1 mg/kg和3 mg/kg，iv)剂量依赖性地降低了尿道括约肌的高频振荡频率。SKF38393或RemoxiPride对膀胱和尿路活动的任何参数都没有显著影响。结论：这些结果表明，棘上部位D2样多巴胺受体的激活可以抑制横纹肌的活动。因此，D2多巴胺受体激活引起的尿路阻力降低可能会加重帕金森病(PD)患者常见的急迫性尿失禁症状。
Aims: To investigate the role of dopamine receptor subtypes in the control of urethral activity. Methods: Simultaneous recordings of intravesical and urethral perfusion pressure (UPP) were performed in rats under urethane anesthesia. Changes in coordinated activity of the bladder and urethral sphincter were examined following intravenous (i.v.), intrathecal (i.t.), or intracerebroventricular (i.c.v.) administration of dopamine D1- and D2-like receptor agonists (SKF38393 and quinpirole, respectively) and antagonists (SCH23390 and remoxipride, respectively). Results: Quinpirole (0.03, 0.1, and 0.3 mg/kg i.v.) dose-dependently decreased baseline urethral pressure to 45.33 +/- 5.8, 33.7 +/- 3.3 (P < 0.05, n = 6), and 27.7 +/- 3.3 cm H2O (P < 0.05, n = 5) from the control value (46.0 +/- 4.0 cm H2O), respectively. i.c.v. injection of quinpirole (1 mu g) decreased baseline urethral pressure to 33.6 +/- 5.0 cm H2O (P < 0.05, n = 4) from the control value (51.4 +/- 4.9 cm H2O) in contrast to the insignificant effects of i.t. administration of the drug (3 mu g). The decrement of baseline pressure induced by quinpirole (0.1 mg/kg i.v.) was suppressed by a-bungarotoxin (BGT), a neuromuscular blocking agent. SCH23390 (1 and 3 mg/kg, i.v.) dose-dependently decreased the frequency of high frequency oscillation (HFO) of the urethral sphincter. SKF38393 or remoxipride did not have significant effects on any parameters of bladder and urethral activity. Conclusions: These results indicate that activation of D2-like dopamine receptors at a supraspinal site can suppress activity of the striated muscle urethral sphincter. Thus, decreased urethral resistance induced by D2 dopamine receptor activation might aggravate urge incontinence symptoms often seen in patients with Parkinson's disease (PD).