Cannabinoid receptor expression in the bladder is altered in detrusor overactivity
Cannabinoid receptor expression in the bladder is altered in detrusor overactivity
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DOI：
10.1007/s00192-015-2802-x
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发表时间：
2016-01-01
影响因子：
1.8
通讯作者：
Tincello, Douglas G.
中科院分区：
文献类型：
--
作者：
Bakali, Evangelia;McDonald, John;Tincello, Douglas G.
免疫组织化学（IHC）证据表明，大麻素受体（CB）在人类膀胱中表达，大麻素激动剂已知可抑制逼尿肌收缩。然而，这种抑制的机制尚不清楚。此外，CB在逼尿肌过度活动（DO）中的作用尚不清楚。本研究的目的是比较正常和DO人膀胱中CB的表达，并进一步表征这些受体。采用聚合酶链反应（PCR）检测膀胱样本中CB转录本的差异。用免疫组化法评估CB蛋白表达差异。免疫荧光法（IF）用于评价CB与神经纤维的共定位。使用大麻素放射配体[H-3]-CP-55,940测量受体密度和结合亲和力。与正常膀胱相比，DO患者尿路上皮中CB1转录本水平较高，而逼尿肌中CB1转录本水平较低。放射性配体结合显示正常人膀胱的CB密度为421 +/- 104 fmol/mg。免疫组化在蛋白质水平上证实了这些发现。IF染色显示CB1与胆碱乙酰转移酶（choline acetyltransferase-, ChAT）阳性神经在逼尿肌共定位，与PGP9.5在尿路上皮和逼尿肌共定位。CB2与ChAT和PGP9.5共同定位于尿路上皮和逼尿肌。DO患者逼尿肌中大麻素受体表达降低，这可能在该疾病的病理生理中发挥作用。CB受体与胆碱能神经的共定位可能表明CB1定位于突触前和突触后末端，可能影响神经递质释放。我们的研究结果表明大麻素激动剂在膀胱过度活跃药物治疗中的潜在作用。
Immunohistochemical (IHC) evidence shows that cannabinoid receptors (CB) are expressed in human bladders and cannabinoid agonists are known to inhibit detrusor contractility. However, the mechanism for this inhibition remains unknown. In addition, the role of CB in detrusor overactivity (DO) is under-investigated. The aim of this study was to compare CB expression in normal and DO human bladders and to further characterise these receptors.Polymer chain reaction (PCR) was used to detect differences in CB transcripts in bladder samples. Differences in CB protein expression was assessed by IHC. Immunofluorescence (IF) was used to evaluate co-localisation of CB with nerve fibres. Receptor density and binding affinity were measured using the cannabinoid radioligand [H-3]-CP-55,940.There were higher levels of CB1 transcripts in the urothelium of patients with DO and lower levels in the detrusor, compared with normal bladders. Radioligand binding revealed CB density of 421 +/- 104 fmol/mg protein in normal human bladders. IHC confirmed these findings at the protein level. IF staining demonstrated co-localisation of CB1 with choline acetyltransferase-(ChAT)-positive nerves in the detrusor and co-localisation with PGP9.5 in both urothelium and detrusor. CB2 was co-localised with both ChAT and PGP9.5 in the urothelium and the detrusor.Cannabinoid receptor expression is reduced in the detrusor of patients with DO, which may play a role in the pathophysiology of the disease. Co-localisation of CB receptors with cholinergic nerves may suggest that CB1, being localised on pre- and postsynaptic terminals, could influence neurotransmitter release. Our findings suggest the potential role of cannabinoid agonists in overactive bladder pharmacotherapy.