Lu Shing-Hwa, Groat William C de, Lin Alex T L, Chen Kuang-Kuo, Chang Luke S
Department of Urology, National Yang-Ming University School of Medicine, Division of Urology, Taipei City Hospital, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2007 Oct;70(10):439-44. doi: 10.1016/s1726-4901(08)70035-2.
To investigate the effect of a selective P2X(3-)P2X(2/3) purinergic receptor antagonist (a-317491) on detrusor hyperreflexia in conscious chronic spinal cord-injured female rats.
Six chronic spinal cord-transected female Sprague-Dawley rats (290-336 g) were used in this study. Spinal transection at the T8-T9 segmental level was performed using aseptic techniques under halothane anesthesia. Fourteen to 16 weeks after spinal transection, A-317491, a selective P2X(3-)P2X(2/3) purinergic receptor antagonist, was administered intravenously in cystometry studies at increasing doses of 0.03, 0.1, 0.3, 1, 3, 10 and 30 micromol/kg at 40-50 minute intervals. Cystometrograms (CMGs) were performed before and after the administration of each dose of the drug.
The continuous filling of CMGs revealed a large number of small-amplitude (> 8 cmH(2)O), non-voiding contractions (NVCs) (average, 9.7 per voiding cycle) preceding voiding contractions (mean amplitude, 31 cmH(2)O; duration, 2.5 minutes), which occurred at an interval of 539 seconds and at a pressure threshold of 5.7 cmH(2)O. When tested in a range of doses (0.03-30 micromol/kg, intravenous), A-317491 in doses between 1 and 30 micromol/kg significantly (p < 0.05) increased the interval between voids by 25%, reduced the number of NVCs by 42-62%, and increased the pressure threshold for voiding by 53-73%, but did not change the amplitude of the duration of the voiding contractions. The effects of the drug were apparent within 10 minutes following administration.
These results indicate that purinergic mechanisms, presumably involving P2X(3) or P2X(2/3) receptors on bladder C-fiber afferent nerves, play an important role in the detrusor hyperreflexia that occurs after spinal cord injury in rats.
研究选择性P2X(3)-P2X(2/3)嘌呤能受体拮抗剂（a-317491）对清醒慢性脊髓损伤雌性大鼠逼尿肌反射亢进的影响。
本研究使用6只慢性脊髓横断的雌性Sprague-Dawley大鼠（体重290-336克）。在氟烷麻醉下采用无菌技术在T8-T9节段水平进行脊髓横断。脊髓横断后14至16周，在膀胱测压研究中静脉注射选择性P2X(3)-P2X(2/3)嘌呤能受体拮抗剂A-317491，剂量递增，分别为0.03、0.1、0.3、1、3、10和30微摩尔/千克，间隔40-50分钟。在每次给药前后进行膀胱测压图（CMG）检查。
CMG的持续充盈显示，在排尿收缩（平均幅度31厘米水柱；持续时间2.5分钟）之前有大量小幅度（>8厘米水柱）的无排尿收缩（NVC）（平均每个排尿周期9.7次），排尿收缩间隔为539秒，压力阈值为5.7厘米水柱。当在一系列剂量（0.03-30微摩尔/千克，静脉注射）范围内进行测试时，1至30微摩尔/千克剂量的A-317491显著（p<0.0
