Expression and function of rat urothelial P2Y receptors
Expression and function of rat urothelial P2Y receptors
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DOI：
10.1152/ajprenal.00321.2006
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发表时间：
2008-04-01
影响因子：
4.2
通讯作者：
Birder, Lori A.
中科院分区：
文献类型：
--
作者：
Chopra, Bikramjit;Gever, Joel;Birder, Lori A.
下尿路的控制和调节部分由嘌呤能信号介导。本研究探讨了P2 Y受体在大鼠膀胱中的分布和功能。应用P2 Y激动剂诱导大鼠尿路上皮细胞内钙升高激动剂效力（pEC（50）+/- SE）等级顺序为ATP（5.10 +/- 0.07）> UTP（4.91 +/- 0.14）> UTP γ S（4.61 +/- 0.16）= ATP γ S（4.70 +/- 0.05）> 2-甲硫基腺苷5 '-二磷酸= 5'-（N-乙基甲酰胺基）腺苷= ADP（< 3.5）。这些激动剂的等级顺序效力表明，尿路上皮细胞功能性表达P2 Y（2）/P2 Y（4）受体，相对缺乏其他P2 Y或腺苷受体的贡献。实时PCR、蛋白质印迹和免疫细胞化学证实了P2 Y（2）和P2 Y（4）在尿路上皮中的表达。免疫细胞化学研究显示，P2 Y2染色在尿路上皮的所有层中表达，P2 Y相对缺失（4）。P2 Y（2）染色也存在于上皮下神经束和逼尿肌平滑肌。发现添加UTP和UTP γ S引起培养的大鼠尿路上皮细胞释放ATP。这些结果表明，培养的大鼠尿路上皮细胞功能表达P2 Y（2）/P2 Y（4）受体。这些受体的激活可能在整个尿路上皮的自分泌和旁分泌信号传导中起作用。这可能导致生物活性介质的释放，例如额外的ATP、一氧化氮和乙酰胆碱，其可以通过作用于上皮下肌成纤维细胞和/或骨盆传入纤维来调节排尿反射。
The control and regulation of the lower urinary tract are partly mediated by purinergic signaling. This study investigated the distribution and function of P2Y receptors in the rat urinary bladder. Application of P2Y agonists to rat urothelial cells evoked increases in intracellular calcium; the rank order of agonist potency (pEC(50) +/- SE) was ATP (5.10 +/- 0.07) > UTP (4.91 +/- 0.14) > UTP gamma S (4.61 +/- 0.16) = ATP gamma S (4.70 +/- 0.05) > 2-methylthio adenosine 5'-diphosphate = 5'-(N-ethylcarboxamido)adenosine = ADP (< 3.5). The rank order potency for these agonists indicates that urothelial cells functionally express P2Y(2)/P2Y(4) receptors, with a relative lack of contribution from other P2Y or adenosine receptors. Real-time PCR, Western blotting, and immunocytochemistry confirmed the expression of P2Y(2) and to a lesser extent P2Y(4) in the urothelium. Immunocytochemical studies revealed expression of P2Y2 staining in all layers of the urothelium, with relative absence of P2Y(4). P2Y(2) staining was also present in suburothelial nerve bundles and underlying detrusor smooth muscle. Addition of UTP and UTP gamma S was found to evoke ATP release from cultured rat urothelial cells. These findings indicate that cultured rat urothelial cells functionally express P2Y(2)/P2Y(4) receptors. Activation of these receptors could have a role in autocrine and paracrine signaling throughout the urothelium. This could lead to the release of bioactive mediators such as additional ATP, nitric oxide, and acetylcholine, which can modulate the micturition reflex by acting on suburothelial myofibroblasts and/or pelvic afferent fibers.