Campeau Lysanne, Füllhase Claudius, Sawada Norifumi, Gratzke Christian, Hedlund Petter, Howlett Allyn C, Andersson Karl-Erik
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Urology, New York University, New York, New York.
Neurourol Urodyn. 2014 Jun;33(5):566-70. doi: 10.1002/nau.22454. Epub 2013 Jul 3.
The contribution of individual CB receptors (CB1 R and CB2 R) to normal micturition has not been clearly defined. Our goal was to study if differences in urodynamic parameters or in vitro bladder contractility can be demonstrated between CB2 R knockout (CB2 RKO) and C57BL/6J control (wild type, WT) mice.
Female WT and CB2 RKO mice underwent bladder catheterization and cystometry was performed after 2 and 3 days. Cystometric evaluations were performed in awake animals without drug administration, and WT were also given HU-308 (CB2 R agonist) followed by AM630 (CB2 R antagonist). Bladders were removed for in vitro assessment of contractile responses to carbachol and electrical field stimulation (EFS).
CB2 RKO mice had significantly higher intercontraction intervals (ICIs), bladder capacity (BC) and compliance (Bcom) than WT controls (P < 0.05). In WT mice, BC and ICI were increased from baseline by HU-308 exposure, and then returned to baseline levels after AM630 administration (P < 0.05). There were no differences in contractility after carbachol or EFS between the groups.
Lack of CB2 R was associated with longer ICI and higher BC and Bcom than its presence (WT controls). This was unexpected since in WT, an increase in BC and ICI from baseline was observed after CB2 R agonist administration, and this action was reversed by a CB2 R antagonist. Since there were no differences in the in vitro responses to carbachol and EFS in bladder strips, it may be speculated that the urodynamic differences are caused by a change in the central nervous micturition control in CB2 RKO animals. Neurourol. Urodynam. 33:566-570, 2014. © 2013 Wiley Periodicals, Inc.
个体大麻素受体（CB1R和CB2R）对正常排尿的作用尚未明确界定。我们的目标是研究在CB2R基因敲除（CB2RKO）小鼠和C57BL/6J对照（野生型，WT）小鼠之间，是否能证明尿动力学参数或体外膀胱收缩性存在差异。
雌性WT和CB2RKO小鼠接受膀胱插管，并在2天和3天后进行膀胱测压。在未给药的清醒动物中进行膀胱测压评估，并且给WT小鼠注射HU-308（CB2R激动剂），随后注射AM630（CB2R拮抗剂）。取出膀胱用于体外评估对卡巴胆碱和电场刺激（EFS）的收缩反应。
CB2RKO小鼠的收缩间期（ICI）、膀胱容量（BC）和顺应性（Bcom）显著高于WT对照（P < 0.05）。在WT小鼠中，暴露于HU-308后BC和ICI从基线水平增加，然后在注射AM630后恢复到基线水平（P < 0.05）。两组之间在卡巴胆碱或EFS刺激后的收缩性没有差异。
与CB2R存在时（WT对照）相比，缺乏CB2R与更长的ICI以及更高的BC和Bcom相关。这是出乎意料的，因为在WT小鼠中，注射CB2R激动剂后观察到BC和ICI从基线水平增加，并且这种作用被CB2R拮抗剂逆转。由于膀胱条带对卡巴胆碱和EFS的体外反应没有差异，推测尿动力学差异是由CB2RKO动物中枢神经系统排尿控制的变化引起的。《神经泌尿学与尿动力学》33:566 - 570，2014年。© 2013威利期刊公司
