Distribution and Function of Cannabinoid Receptors 1 and 2 in the Rat, Monkey and Human Bladder

Distribution and Function of Cannabinoid Receptors 1 and 2 in the Rat, Monkey and Human Bladder
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DOI:
10.1016/j.juro.2008.11.079
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发表时间:
2009-04-01
期刊:
影响因子:
6.6
通讯作者:
Andersson, Karl-Erik
Andersson, Karl-Erik
中科院分区:
医学1区
文献类型:
--
作者:
Gratzke, Christian;Streng, Tomi;Andersson, Karl-Erik

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目的:研究大麻素受体1和2亚型在不同物种逼尿肌中的分布,并研究大麻素受体1和2激动剂对膀胱功能的影响。材料与方法:采用Western blot和免疫组化方法研究大麻素受体1和2在大鼠、猴和人逼尿肌组织中的表达。用降钙素基因相关肽(euro - diagnotica,马尔默,瑞典)和瞬时受体电位香草蛋白1对感觉神经标记物进行共染色,用VAChT (Santa Cruz Biotechnology, Santa Cruz, California)对胆碱能神经标记物进行共染色。记录内源性大麻素受体1和2激动剂anandamide (Sigma (R))和大麻素受体1和2激动剂CP55,940 (Sigma)在清醒大鼠离体逼尿肌和造囊术中的作用。结果:粘膜中大麻素受体2的表达高于逼尿肌,而大麻素受体1的表达低于逼尿肌。与逼尿肌相比,在上皮下观察到大量含有大麻素受体2的神经也表达瞬时受体电位香草素1或降钙素基因相关肽。含有大麻素受体2和VAChT的神经纤维位于逼尿肌。anandamide和CP55,940均不影响离体逼尿肌缩醛(Sigma)收缩。10 μ M anandamide可增强神经收缩,10 μ AM CP55,940可减弱神经收缩
Purpose: We investigated the distribution of cannabinoid receptor subtypes 1 and 2 in the detrusor of different species and studied the effects of cannabinoid receptor 1 and 2 agonists on bladder function.Materials and Methods: Cannabinoid receptor 1 and 2 expression was studied with Western blot and immunohistochemistry in rat, monkey and human detrusors. Co-staining was done for markers of sensory nerves using calcitonin gene-related peptide (Euro-Diagnostica, Malmo, Sweden) and transient receptor potential vanilloid 1, and for cholinergic nerves using VAChT (Santa Cruz Biotechnology, Santa Cruz, California). Actions of the endogenous cannabinoid receptor-1 and 2 agonist anandamide (Sigma (R)), and the cannabinoid receptor 1 and 2 agonist CP55,940 (Sigma) on isolated detrusor and during cystometry in conscious rats were recorded.Results: Higher expression of cannabinoid receptor 2 but not cannabinoid receptor 1 was noted in the mucosa than in the detrusor. Compared to the detrusor larger amounts of cannabinoid receptor 2 containing nerves that also expressed transient receptor potential vanilloid 1 or calcitonin gene-related peptide were observed in the suburothelium. Nerve fibers containing cannabinoid receptor 2 and VAChT were located in the detrusor. Neither anandamide nor CP55,940 affected isolated detrusor carbachol (Sigma) contractions. Nerve contractions were enhanced by 10 mu M anandamide and decreased by 10 AM CP55,940 (P