Alteration of muscarinic and purinergic receptors in urinary bladder of rats with cyclophosphamide-induced interstitial cystitis
Alteration of muscarinic and purinergic receptors in urinary bladder of rats with cyclophosphamide-induced interstitial cystitis
复制标题
DOI：
10.1016/j.neulet.2008.02.065
复制
发表时间：
2008-05-02
影响因子：
2.5
通讯作者：
Yamada, Shizuo
中科院分区：
文献类型：
--
作者：
Kageyama, Aiko;Fujino, Tomomi;Yamada, Shizuo
我们对环磷酰胺 (CYP) 治疗的大鼠膀胱中的毒蕈碱和嘌呤能受体以及尿动力学参数进行了表征，以阐明间质性膀胱炎 (IC) 病理生理学的机制。与对照大鼠相比，CYP治疗组大鼠的膀胱肾中，排尿间隔和排尿量显着减少（分别为55％和77％），排尿频率和基础压力显着增加（分别为3倍和2.3倍）。尿动力学参数的这些变化可能是 CYP 治疗大鼠逼尿肌过度活动的特征。与对照大鼠相比，CYP治疗大鼠膀胱中[N-甲基-H-3]东莨菪碱甲基氯化物（[H-3]NMS）和αβ-亚甲基ATP[2,8-H-3]四钠盐（[H-3]αβ-MeATP）特异性结合的最大结合位点（B-max）显着减少（分别为43％和31％）。另一方面，CYP 处理并未显着改变两种放射性配体的表观解离常数 (K-d)。抗毒蕈碱剂（奥昔布宁、托特罗定、达非那新和 AF-DX 116）抑制膀胱 [H-3]NMS 结合的 K-i 值在对照大鼠和 CYP 治疗大鼠之间没有显着差异。 CYP 治疗大鼠中嘌呤能拮抗剂 (A-317491, PPADS) 抑制膀胱 [H-3]α beta-MeATP 结合的抑制常数 (K-i) 显着高于对照大鼠。总之，CYP 治疗已被证明会导致大鼠膀胱中药理学相关（毒蕈碱和嘌呤能）受体的下调。因此，本研究提供了进一步的药理学证据，表明毒蕈碱和嘌呤能机制均对 IC 引起的泌尿功能障碍有显着影响。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
We characterized muscarnic and purinergic receptors and Urodynamic parameters in the bladder of cyclophosphamide (CYP)-treated rats to clarify the mechanisms involved in the pathophysiology of interstitial cystitis (IC). In the cystornetry of CYP-treated rats compared with control rats, the micturition interval and micturition volume were significantly (55% and 77%, respectively) decreased and the frequency of micturition and basal pressure were significantly (3 and 2.3 times, respectively) increased. These changes in urodynamic parameters may characterize the detrusor overactivity occurring in CYP-treated rats. The maximal number of binding sites (B-max) for specific binding of [N-methyl-H-3]scopolamine methyl chloride ([H-3]NMS) and alpha beta-methylene ATP [2,8-H-3]tetrasodium salt ([H-3]alpha beta-MeATP) was significantly (43% and 31%, respectively) decreased in the bladder of CYP-treated rats compared with control rats. On the other hand, the apparent dissociation constant (K-d) for neither radioligand was significantly altered by the CYP treatment. K-i value for the inhibition of bladder [H-3]NMS binding by antimuscarinic agents (oxybutynin, tolterodine, darifenacin, and AF-DX 116) did not differ significantly between control and CYP-treated rats. The inhibition constant (K-i) for the inhibition of bladder [H-3]alpha beta-MeATP binding by purinergic antagonists (A-317491, PPADS) was significantly higher in CYP-treated rats than control rats. In conclusion, CYP treatment has been shown to cause down-regulation of pharmacologically relevant (muscarinic and purinergic) receptors in the bladder of rats. Thus, the present study offers further pharmacological evidence that both muscarinic and purinergic mechanisms contribute significantly to the urinary dysfunction due to IC. (C) 2008 Elsevier Ireland Ltd. All rights reserved.