Kakizaki H, Yoshiyama M, Roppolo J R, Booth A M, De Groat W C
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
J Pharmacol Exp Ther. 1998 Apr;285(1):22-7.
This study was undertaken to evaluate the role of glutamate receptors at spinal synapses on the ascending limb of the micturition reflex. In urethane-anesthetized female rats, a tungsten electrode was inserted stereotaxically into the dorsal part of the rostral pons to record field potentials which were evoked by electrical stimulation of the pelvic nerve (PLN) (1-15 V, 0.05 ms pulse duration at 100-300 Hz, 5-30 ms train duration). The effects of glutamate receptor antagonists administered intrathecally (i.t.) on the PLN-evoked field potentials in the dorsal part of the rostral brainstem were examined. PLN stimulation evoked short latency (10-22 ms) negative field potentials (85 +/- 4 microV) in a limited area of the dorsal part of the rostral pons (bregma -9.0 to -8.4, L 0.5 to 1. 5, H 4.2 to 5.4). The i.t. administration of LY215490 (0.1-30 microg), a competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, reduced the amplitude of the evoked potentials in a dose-dependent manner; 84 +/- 6%, 59 +/- 11% (P < .001), 31 +/- 10% (P < .001), 17 +/- 9% (P < .001) of control after 0.1, 1, 10, 30 microg of LY215490, respectively. The i.t. administration of MK-801 (1-100 microg), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, also reduced the amplitude of the evoked potentials in a dose-dependent manner; 93 +/- 21%, 76 +/- 14%, 52 +/- 9% (P < .001), 39 +/- 9% (P < .001) of control after 1, 10, 30, 100 microg of MK-801, respectively. Combined administration of LY215490 (0.1 microg) and MK-801 (1 microg), in doses which individually did not elicit a significant effect, markedly reduced the amplitude of the evoked potentials (27 +/- 9% of control, P = . 0002). These results suggest that AMPA and NMDA glutamatergic synaptic mechanisms play a key role in the spinal processing of afferent input from the bladder and that these mechanisms function synergistically in the ascending limb of the spinobulbospinal micturition reflex pathway.
本研究旨在评估谷氨酸受体在排尿反射上升支脊髓突触中的作用。在乌拉坦麻醉的雌性大鼠中，将钨电极立体定位插入延髓前部的背侧，记录由电刺激盆神经（PLN）（1-15V，0.05ms脉冲持续时间，100-300Hz，5-30ms串刺激持续时间）诱发的场电位。研究了鞘内注射（i.t.）谷氨酸受体拮抗剂对延髓前部背侧PLN诱发场电位的影响。PLN刺激在延髓前部背侧的有限区域（前囟-9.0至-8.4，L0.5至1.5，H4.2至5.4）诱发短潜伏期（10-22ms）负性场电位（85±4μV）。鞘内注射竞争性α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体拮抗剂LY215490（0.1-30μg）以剂量依赖方式降低诱发电位的幅度；分别给予0.1、1、10、30μg LY215490后，诱发电位幅度分别为对照组的84±6%、59±11%（P<.001）、31±10%（P<.001）、17±9%（P<.001）。鞘内注射非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801（1-100μg）也以剂量依赖方式降低诱发电位的幅度；分别给予1、10、30、100μg MK-801后，诱发电位幅度分别为对照组的93±21%、76±14%、52±9%（P<.001）、39±9%（P<.001）。联合给予单独使用时无显著作用剂量的LY215490（0.1μg）和MK-801（1μg），可显著降低诱发电位的幅度（为对照组的27±9%，P=.0002）。这些结果表明，AMPA和NMDA谷氨酸能突触机制在膀胱传入输入的脊髓处理中起关键作用，且这些机制在脊髓-延髓-脊髓排尿反射通路的上升支中协同发挥作用。
