Roles of glutamatergic and serotonergic mechanisms in reflex control of the external urethral sphincter in urethane-anesthetized female rats

Roles of glutamatergic and serotonergic mechanisms in reflex control of the external urethral sphincter in urethane-anesthetized female rats
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DOI:
10.1152/ajpregu.00780.2005
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发表时间:
2006-07-01
影响因子:
2.8
通讯作者:
de Groat, William C.
de Groat, William C.
中科院分区:
医学3区
文献类型:
--
作者:
Chang, Hui-Yi;Cheng, Chen-Li;de Groat, William C.

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本研究的目的是探讨反射机制,介导膀胱和尿道外括约肌(EUS)的协调,在麻醉的雌性SD大鼠。我们研究了电刺激盆神经传入轴突引起的EUS反射(骨盆EUS反射)的特性。观察了膀胱扩张和给药肾上腺素能或肾上腺素能受体激动剂或拮抗剂引起的反射变化。反射由早期反应(ER,18- 22-ms潜伏期)和晚期长持续时间(> 100-ms潜伏期)反应(LR)组成,后者由20- 160-ms爆发间隔的活动爆发组成。在一些实验中,还确定了具有中间(40- 70-ms)潜伏期的反射。在膀胱排空的情况下,在大多数实验中检测到ER,但未检测到LR。膀胱扩张时LR明显增强。在T-8-T-9脊髓横断后,ER仍然存在,但LR被取消。N-甲基-D-天冬氨酸受体拮抗剂MK-801(0.3 mg/kg iv)使ER和LR分别显著降低75%和35%,而α-氨基-5-甲基异恶唑-4-丙酸酯受体拮抗剂LY-215490(3 mg/ kg iv)仅分别降低18%和14%。5-羟色胺(5-HT 1A)受体激动剂8-羟基-2-(二丙氨基)-四氢萘(1 mg/ kg iv)增强自发EUS活动和骨盆EUS反射。WAY-100635(0.1-1 mg/kg iv)是一种5-HT 1A拮抗剂,可逆转8-羟基-2-(二正丙基氨基)四氢萘的作用,并抑制EUS活性和骨盆EUS反射。这些结果表明,在大鼠膀胱括约肌协调的反射通路中,β-amatergic和β-aminergic机制是重要的。
This study was conducted to examine reflex mechanisms that mediate urinary bladder and external urethral sphincter (EUS) coordination in urethane-anesthetized female Sprague-Dawley rats. We investigated the properties of EUS reflexes elicited by electrical stimulation of pelvic nerve afferent axons (pelvic-EUS reflex). The changes in the reflexes induced by bladder distension and administration of agonists or antagonists for glutamatergic or serotonergic receptors were examined. The reflexes consisted of an early response (ER, 18- to 22-ms latency) and a late, long-duration (> 100-ms latency) response (LR), which consisted of bursts of activity at 20- to 160-ms interburst intervals. In a few experiments, a reflex with an intermediate (40- to 70-ms) latency was also identified. With the bladder empty, the ER, but not the LR, was detected in the majority of experiments. The LR was markedly enhanced when the bladder was distended. The ER remained, but the LR was abolished, after spinal cord transection at T-8-T-9. The ER and LR were significantly decreased 75 and 35%, respectively, by the N-methyl-D-aspartate receptor antagonist MK-801 (0.3 mg/kg iv), but only decreased 18 and 14%, respectively, by the alpha-amino-5-methylisoxazole-4-propionate receptor antagonist LY-215490 ( 3 mg/ kg iv). The serotonin (5-HT1A) receptor agonist 8-hydroxy-2-(dinpropylamino)-tetralin ( 1 mg/ kg iv) enhanced spontaneous EUS activity and the pelvic-EUS reflex. WAY-100635 (0.1-1 mg/kg iv), a 5-HT1A antagonist, reversed the effect of 8-hydroxy-2-(di-n-propylamino)tetralin and suppressed EUS activity and the pelvic-EUS reflex. These results indicate that glutamatergic and serotonergic mechanisms are important in the reflex pathways underlying bladder-sphincter coordination in rats.