Potential for control of detrusor smooth muscle spontaneous rhythmic contraction by cyclooxygenase products released by interstitial cells of Cajal.
Potential for control of detrusor smooth muscle spontaneous rhythmic contraction by cyclooxygenase products released by interstitial cells of Cajal.
复制标题
控制cajal的间质细胞释放的环氧合酶产物产物来控制迫害者平滑肌自发节奏收缩的潜力。
DOI：
10.1111/j.1582-4934.2009.00714.x
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Ratz PH
中科院分区：
文献类型：
--
作者：
Collins C;Klausner AP;Herrick B;Koo HP;Miner AS;Henderson SC;Ratz PH
Cajal间质细胞（Interstitial cells of Cajal，ICCs）是上尿路和尿道的起搏细胞，但其在膀胱中的作用尚不清楚。我们检验了ICCs表达环氧合酶（考克斯）以及考克斯产物（甘草素）是无尿道炎兔膀胱条自发节律性收缩（SRC）的原因的假设。10 μM消炎痛和布洛芬（非选择性考克斯抑制剂）可消除SRC。SRC受到选择性考克斯-1（SC-560和FR-122047）和考克斯-2抑制剂（NS-398和LM-1685）、PGE-2受体（EP）选择性拮抗剂SC-51089以及血栓烷受体（TP）选择性拮抗剂ICI-192，605和SQ-29，548的浓度依赖性抑制。PGF-2α受体（FP）部分激动剂/拮抗剂AL-8810可抑制SRC约50%。SC-51089、考克斯抑制剂和TP受体拮抗剂的最大抑制率分别为90%、80-85%和70%。在布洛芬消除SRC的情况下，PGE-2、硫前列酮、米索前列醇、PGF-2α和U-46619（血栓烷模拟物）引起模仿SRC的节律性收缩。荧光免疫组化结合激光共聚焦显微镜显示c-Kit和波形蛋白共定位于逼尿肌平滑肌束周围的间质细胞，表明兔膀胱中存在广泛的ICC。ICC对考克斯-1和波形蛋白以及考克斯-2和波形蛋白的共定位支持ICC是兔膀胱中表达两种考克斯亚型的主要细胞类型的假设。这些数据共同表明，ICC似乎是一个重要的来源，可能发挥作用，在SRC的监管。对肾上腺素依赖性SRC的进一步研究可能为应用新的治疗方法治疗导致膀胱过度活动症的疾病创造机会。
Interstitial cells of Cajal (ICCs) have been identified as pacemaker cells in the upper urinary tract and urethra, but the role of ICCs in the bladder remains to be determined. We tested the hypotheses that ICCs express cyclooxygenase (COX), and that COX products (prostaglandins), are the cause of spontaneous rhythmic contraction (SRC) of isolated strips of rabbit bladder free of urothelium. SRC was abolished by 10 μM indomethacin and ibuprofen (non-selective COX inhibitors). SRC was concentration-dependently inhibited by selective COX-1 (SC-560 and FR-122047) and COX-2 inhibitors (NS-398 and LM-1685), and by SC-51089, a selective antagonist for the PGE-2 receptor (EP) and ICI-192,605 and SQ-29,548, selective antagonists for thromboxane receptors (TP). The partial agonist/antagonist of the PGF-2α receptor (FP), AL-8810, inhibited SRC by ∼50%. Maximum inhibition was ∼90% by SC-51089, ∼80–85% by the COX inhibitors and ∼70% by TP receptor antagonists. In the presence of ibuprofen to abolish SRC, PGE-2, sulprostone, misoprostol, PGF-2α and U-46619 (thromboxane mimetic) caused rhythmic contractions that mimicked SRC. Fluorescence immunohistochemistry coupled with confocal laser scanning microscopy revealed that c-Kit and vimentin co-localized to interstitial cells surrounding detrusor smooth muscle bundles, indicating the presence of extensive ICCs in rabbit bladder. Co-localization of COX-1 and vimentin, and COX-2 and vimentin by ICCs supports the hypothesis that ICCs were the predominant cell type in rabbit bladder expressing both COX isoforms. These data together suggest that ICCs appear to be an important source of prostaglandins that likely play a role in regulation of SRC. Additional studies on prostaglandin-dependent SRC may generate opportunities for the application of novel treatments for disorders leading to overactive bladder.