Endocannabinoids in Bladder Sensory Mechanisms in Health and Diseases.
Endocannabinoids in Bladder Sensory Mechanisms in Health and Diseases.
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DOI：
10.3389/fphar.2021.708989
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zagorodnyuk V
中科院分区：
文献类型：
--
作者：
Christie S;Brookes S;Zagorodnyuk V
最近大麻素研究的激增可能是由于几个司法管辖区的立法变化，以及批准使用大麻素治疗一些慢性疾病。内源性大麻素主要作用于大麻素受体1和2 (CBR1和CBR2)，这两种受体在膀胱中主要通过尿路上皮和轴突以及运动和感觉神经元的末梢表达。越来越多的证据表明，在正常生理条件下，内源性大麻素系统在尿液储存和排尿过程中构成性地下调膀胱感觉功能。同样，外源性大麻素激动剂具有强大的调节作用，内源性大麻素失活抑制剂也是如此。结果表明大麻素在治疗性改善膀胱过度活跃和膀胱疼痛综合征的下尿路症状方面具有很高的潜力。尽管对传出神经的作用使解释复杂化，但至少部分可能是通过对感觉神经的作用介导的。膀胱的感觉神经支配是复杂的，至少有八类。我们对内源性大麻素和合成激动剂对不同类型膀胱感觉神经元的作用的了解还存在很大的差距。在膀胱疾病动物模型中，选择性大麻素受体2激动剂和/或外周限制性合成大麻素受体1激动剂对膀胱感觉神经元的作用有待进一步研究。这些没有中枢神经系统精神作用的新疗法具有巨大的潜力，并且可以避免目前治疗膀胱过度活动和膀胱疼痛综合征的许多副作用。
The recent surge in research on cannabinoids may have been fueled by changes in legislation in several jurisdictions, and by approval for the use of cannabinoids for treatment of some chronic diseases. Endocannabinoids act largely, but not exclusively on cannabinoid receptors 1 and 2 (CBR1 and CBR2) which are expressed in the bladder mainly by the urothelium and the axons and endings of motor and sensory neurons. A growing body of evidence suggests that endocannabinoid system constitutively downregulates sensory bladder function during urine storage and micturition, under normal physiological conditions. Similarly, exogenous cannabinoid agonists have potent modulatory effects, as do inhibitors of endocannabinoid inactivation. Results suggest a high potential of cannabinoids to therapeutically ameliorate lower urinary tract symptoms in overactive bladder and painful bladder syndromes. At least part of this may be mediated via effects on sensory nerves, although actions on efferent nerves complicate interpretation. The sensory innervation of bladder is complex with at least eight classes identified. There is a large gap in our knowledge of the effects of endocannabinoids and synthetic agonists on different classes of bladder sensory neurons. Future studies are needed to reveal the action of selective cannabinoid receptor 2 agonists and/or peripherally restricted synthetic cannabinoid receptor 1 agonists on bladder sensory neurons in animal models of bladder diseases. There is significant potential for these novel therapeutics which are devoid of central nervous system psychotropic actions, and which may avoid many of the side effects of current treatments for overactive bladder and painful bladder syndromes.
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影响因子：
6.6
作者：
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