Functional and Immunohistochemical Characterization of CB1 and CB2 Receptors in Rat Bladder
Functional and Immunohistochemical Characterization of CB1 and CB2 Receptors in Rat Bladder
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DOI：
10.1016/j.urology.2008.03.044
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发表时间：
2008-11-01
期刊：
影响因子：
2.1
通讯作者：
Tyagi, Pradeep
中科院分区：
文献类型：
--
作者：
Hayn, Matthew H.;Ballesteros, Inmaculada;Tyagi, Pradeep
目的：研究大鼠膀胱组织中CB 1和CB 2受体的分布，并观察CB 1/CB 2受体激动剂阿佳酸（ajulemic acid，AJA）对化学诱发的感觉神经肽降钙素基因相关肽（calcitonin gene-related peptide，CGRP）释放的影响。辣椒素（30 nM）和腺苷三磷酸（10 μ M）用于在存在或不存在AJA的情况下激发CGRP释放。使用拮抗剂测定AJA对CB 1和CB 2受体的特异性。结果免疫荧光法显示CB 1和CB 2受体在膀胱内的分布。平均基线CGRP释放为605 +/- 62 pg/g膀胱重量，AJA对CGRP释放没有影响。添加三磷酸腺苷/辣椒素显著增加CGRP释放，与基线相比增加了44%（P <0.05），并且与对照相比，AJA应用显著降低了CGRP释放，减少了29%（P <0.05）。CB 1和CB 2受体拮抗剂AM 251和AM 630可分别逆转AJA对CGRP释放的抑制作用，使其分别增加40%和38%.CONCLUSIONS CB 1和CB 2受体定位于大鼠膀胱尿路上皮，AJA通过作用于CB 1和CB 2受体抑制CGRP的释放。这些发现为膀胱疼痛综合征/间质性膀胱炎的评价和治疗研究确定了一种潜在的新途径。泌尿学72：1174-1178，2008。(C)2008年爱思唯尔公司
OBJECTIVES To determined the localization of CB1 and CB2 receptors in rat bladder and investigate the effect of a mixed CB1/CB2 receptor agonist, ajulemic acid (AJA), on chemically evoked release of the sensory neuropeptide calcitonin gene-retated peptide (CGRP).METHODS Whole rat bladders were incubated in a series of tissue baths containing physiologic salt solution to measure baseline CGRP release by enzyme immunoassay. Capsaicin (30 nM) and adenosine triphosphate (10 mu M) were used to provoke CGRP release in the presence or absence of AJA. Specificity of AJA for CB1 and CB2 receptors was determined using antagonists. Localization was determined by immunofluorescence for CB1 and CB2 receptors in fixed bladders.RESULTS Immunofluorescence, showed the localization of CB1 and CB2 receptors in the bladder. Mean baseline CGRP release was 605 +/- 62 pg/g of bladder weight, and AJA had no effect on CGRP release. The addition of adenosine triphosphate/capsaicin significantly increased the CGRP release over baseline, by 44% (P < .05), and AJA application significantly decreased CGRP release, by 29% compared with controls (P < .05). The CB1 and CB2 antagonists AM 251 and AM 630, respectively, reversed the blunting effect of AJA on evoked CGRP release, resulting in an increase of 40% and 38% over baseline, respectively.CONCLUSIONS CB1 and CB2 receptors are localized in the urothelium of rat bladder, and application of AJA inhibits the evoked release of CGRP by acting on CB1 and CB2 receptors. These findings identify a potential new pathway for study in the evaluation and treatment of painful bladder syndrome/interstitial cystitis. UROLOGY 72: 1174-1178, 2008. (C) 2008 Elsevier Inc.