Department of Clinical and Experimental Pharmacology, Lund University, Lund, Sweden.
Eur Urol. 2010 Jun;57(6):1093-100. doi: 10.1016/j.eururo.2010.02.027. Epub 2010 Mar 1.
Cannabinoid (CB) receptors may be involved in the control of bladder function; the role of CB receptor subtypes in micturition has not been established.
Our aim was to evaluate the effects of cannabinor, a novel CB2 receptor agonist, on rat bladder function.
DESIGN, SETTING, AND PARTICIPANTS: Sprague Dawley rats were used. Distribution of CB2 receptors in sensory and cholinergic nerves of the detrusor was studied. Selectivity of cannabinor for human and rat CB receptors was evaluated. Effects of cannabinor on rat detrusor and micturition were investigated.
Immunohistochemistry, radioligand binding, tritium outflow assays, organ bath studies of isolated bladder tissue, and cystometry in awake rats were used.
CB2 receptor immunoreactivity was expressed in the urothelium and in sensory and cholinergic bladder nerves. Cannabinor exhibited similar binding at human and rat CB2 receptors and a 321-fold functional selectivity for the CB2 receptor versus the CB1 receptor. Cannabinor had no effect on isolated detrusor muscle function. In vivo, cannabinor 3.0mg/kg increased micturition intervals and volumes by 52% (p<0.05) and 96% (p<0.01), respectively, and increased threshold and flow pressures by 73% (p<0.01) and 49% (p<0.001), respectively. Cannabinor 0.3 or 1.0mg/kg or vehicle did not affect urodynamic parameters.
Considering that CB2 receptors are localized on sensory nerves and on the urothelium and that cannabinor had effects on "afferent" urodynamic parameters, peripheral CB2 receptors may be involved in sensory functions of rat micturition. Effects of cannabinor on cholinergic nerve activity in normal bladder tissue appear to be limited.
大麻素（CB）受体可能参与了膀胱功能的控制；然而，CB 受体亚型在排尿中的作用尚未确定。
我们旨在评估新型 CB2 受体激动剂大麻诺的对大鼠膀胱功能的影响。
设计、地点和参与者：使用 Sprague Dawley 大鼠。研究了 CB2 受体在逼尿肌感觉神经和胆碱能神经中的分布。评估了大麻诺对人和大鼠 CB 受体的选择性。研究了大麻诺对大鼠逼尿肌和排尿的影响。
使用免疫组织化学、放射性配体结合、氚外流测定、离体膀胱组织器官浴研究和清醒大鼠膀胱测压。
CB2 受体免疫反应性在尿路上皮和感觉神经和胆碱能膀胱神经中表达。大麻诺在人源和大鼠 CB2 受体上表现出相似的结合，并对 CB2 受体相对于 CB1 受体具有 321 倍的功能选择性。大麻诺对离体逼尿肌功能没有影响。在体内，大麻诺 3.0mg/kg 使排尿间隔和尿量分别增加 52%（p<0.05）和 96%（p<0.01），并分别使阈值和流量压力增加 73%（p<0.01）和 49%（p<0.001）。大麻诺 0.3 或 1.0mg/kg 或载体对尿动力学参数没有影响。
鉴于 CB2 受体定位于感觉神经和尿路上皮，并且大麻诺对“传入”尿动力学参数有影响，因此外周 CB2 受体可能参与了大鼠排尿的感觉功能。大麻诺对正常膀胱组织中胆碱能神经活性的影响似乎有限。
