Effects of CL316,243, a β3-Adrenoceptor Agonist, and Intravesical Prostaglandin E2 on the Primary Bladder Afferent Activity of the Rat
Effects of CL316,243, a β3-Adrenoceptor Agonist, and Intravesical Prostaglandin E2 on the Primary Bladder Afferent Activity of the Rat
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DOI：
10.1002/nau.20826
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发表时间：
2010-01-01
影响因子：
2
通讯作者：
Wyndaele, Jean-Jacques
中科院分区：
文献类型：
--
作者：
Aizawa, Naoki;Igawa, Yasuhiko;Wyndaele, Jean-Jacques
目的：已经表明β（3）-肾上腺素能受体（β（3）-AR）激动剂不仅影响支配膀胱的传出通路，而且影响支配膀胱的传入通路。此外，前列腺素E-2（PGE（2））会导致清醒大鼠膀胱过度活跃。我们研究了β（3）-AR激动剂（CL 316，243; CL）和PGE（2）对初级膀胱传入神经单纤维活动的直接影响。方法：使用雌性Sprague-Dawley大鼠。在氨基甲酸乙酯麻醉下，通过电刺激左骨盆神经和膀胱扩张来识别主要源自膀胱的单个神经纤维，并通过传导速度（2.5 m/sec）将其分为A δ纤维或C纤维。重复三次恒定膀胱充盈的传入活动测量，第三次测量作为基线观察。然后，静脉内给予CL（10 μ g/kg）或其赋形剂。此后，膀胱内滴注10（-4）M PGE（2）或生理盐水，并记录另外三个周期。结果：34只大鼠共分离出43条单纤维（A δ纤维20条，C纤维23条）。静脉内施用CL而不是媒介物显著降低了A δ-纤维而不是C-纤维响应于用盐水填充膀胱的活动。膀胱灌注PGE（2）可显著增加C纤维活性，但对A δ纤维活性无影响。CL预处理可抑制PGE（2）诱导的C-纤维活性增加。结论：目前的结果清楚地表明，β（3）-AR激动剂，CL 316，243，可以抑制大鼠的初级膀胱传入的机械敏感性A δ纤维，但不抑制C纤维。此外，β（3）-AR激动剂可抑制PGE（2）诱导的C纤维亢进。Neurorol。Urodynam。29：771 - 776，2010. (C)2010 Wiley-Liss，Inc.
Aims: It has been suggested that beta(3)-adrenoceptor (beta(3)-AR) agonists affect not only the efferent but also the afferent pathways innervating the bladder. In addition, prostaglandin E-2 (PGE(2)) causes bladder hyperactivity in conscious rats. We investigated the direct effects of a beta(3)-AR agonist (CL316,243; CL) and PGE(2) on single fiber activities of the primary bladder afferent nerves. Methods: Female Sprague-Dawley rats were used. Under urethane anesthesia, a single nerve fiber primarily originating from the bladder was identified by electrical stimulation of the left pelvic nerve and by bladder distention, and was divided by conduction velocity (2.5 m/sec) as A delta-fiber or C-fiber. The afferent activity measurements with constant bladder filling were repeated three times and the third measurement served as the base-line observation. Then, CL (10 mu g/kg) or its vehicle was administrated intravenously. Thereafter, 10(-4)M of PGE(2) or saline was instilled intravesically and another three cycles recorded. Results: Forty-three single afferent fibers (A delta-fibers: n = 20, C-fibers: n = 23) were isolated from 34 rats. Intravenous administration of CL, but not vehicle, significantly decreased A delta-fiber, but not C-fiber, activities in response to bladder filling with saline. Intravesical instillation of PGE(2) significantly increased C-fiber activities, but not A delta-fiber activities. The PGE(2)-induced increase in C-fiber activities was inhibited by pretreatment with CL. Conclusions: The present results clearly demonstrate that the beta(3)-AR agonist, CL316,243, can inhibit the mechanosensitive A delta-fibers, but not the C-fibers, of the primary bladder afferents of the rat. In addition, the beta(3)-AR agonist can inhibit PGE(2)-induced C-fiber hyperactivity. Neurourol. Urodynam. 29:771-776, 2010. (C) 2010 Wiley-Liss, Inc.