Effects of cannabinoid receptor activation by CP55,940 on normal bladder function and irritation-induced bladder overactivity in non-awake anaesthetised rats
Effects of cannabinoid receptor activation by CP55,940 on normal bladder function and irritation-induced bladder overactivity in non-awake anaesthetised rats
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DOI：
10.1007/s00192-016-2984-x
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发表时间：
2016-09-01
影响因子：
1.8
通讯作者：
Tincello, Douglas G.
中科院分区：
文献类型：
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作者：
Bakali, Evangelia;Mbaki, Yvonne;Tincello, Douglas G.
本研究旨在评价CP 55，940对正常膀胱功能的体内作用，并检查其是否抑制膀胱中由伤害性刺激诱导的尿频。大麻素受体（CBR）活性可能参与膀胱功能的调节。然而，CBR亚型在排尿中的作用尚未确定。在尿烷麻醉下进行膀胱测压，以评价膀胱内递送CP 55，940与或不与CB 1拮抗剂AM 251或CB 2拮抗剂AM 630一起施用对雌性大鼠膀胱功能的影响。用醋酸引起的大鼠膀胱刺激模型，观察了CP_（55），940的作用，发现CP_（55），940可使排尿间隔（MI）和膀胱容量（BC）增加52%（P < 0.05），最大排尿压（MP）降低25%（P < 0.05）。在CP 55，940给药前用AM 251或AM 630预处理可防止CP 55，940诱导的MI、BC增加和MP降低。醋酸诱导的排尿频率可由MI的减少证明，并被CP 55，940抑制。CP 55，940降低膀胱活动和由伤害性刺激诱导的排尿频率，可能是通过抑制膀胱传入活动。CP 55，940的作用被两种CBR拮抗剂消除。这些数据暗示了内源性大麻素系统在大鼠膀胱机械传入功能中的作用。此外，我们的研究结果表明，CP 55，940逆转膀胱过度活动症模型中的排尿频率，这表明它可能是下尿路症状患者的有效治疗方法。
This study was designed to evaluate the effects of CP55,940 on normal bladder function in vivo and examine whether it suppresses urinary frequency induced by nociceptive stimuli in the bladder. Cannabinoid receptor (CBR) activity may be involved in the regulation of bladder function. However, the role of CBR subtypes in micturition has yet to be established. CP55,940 is a synthetic analogue of tetrahydrocannabidiol, which is a psychoactive ingredient of the Cannabis plant.Cystometry under urethane anaesthesia was performed to evaluate the effect of intravesical delivery of CP55,940 with or without administration of CB1 antagonist AM251 or CB2 antagonist AM630 on bladder function in female rats. The effects of CP55,940 were also examined in rats with urinary irritation induced by intravesical infusion of acetic acid.Infusion of CP55,940 significantly (p < 0.05) increased micturition interval (MI) and bladder capacity (BC) by 52 % and decreased maximal voiding pressure (MP) by 25 %. Pretreatment with AM251 or AM630 before CP55,940 administration prevented CP55,940-induced increases in MI, BC and reduced MP. Acetic acid induced urinary frequency as evidenced by a reduction in MI and was suppressed by CP55,940.CP55,940 decreases bladder activity and urinary frequency induced by nociceptive stimuli, probably by suppression of bladder afferent activity. Effects of CP55,940 were abolished by both CBR antagonists. This data implicates a role for the endocannabinoid system in bladder mechanoafferent function in rats. In addition, our results show that CP55,940 reverses urinary frequency exemplified in an overactive bladder model, suggesting it could be an effective treatment for patients with lower urinary tract symptoms.