P2Y receptors of MDCK cells: Epithelial cell regulation by extracellular nucleotides
P2Y receptors of MDCK cells: Epithelial cell regulation by extracellular nucleotides
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DOI：
10.1046/j.1440-1681.2001.03452.x
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发表时间：
2001-04-01
影响因子：
2.9
通讯作者：
Post, SR
中科院分区：
文献类型：
--
作者：
Insel, PA;Ostrom, RS;Post, SR
1. Madin-Darby犬肾（MDCK）细胞是一种来源于远端小管/集合管的分化良好的肾上皮细胞系，通过改变离子通量和花生四烯酸衍生产物（特别是前列腺素E-2（PGE（2）的产生来响应细胞外核苷酸。我们的工作已经确定了参与这种反应的受体和信号事件。我们已经发现在MDCK-D-1细胞中至少三种P2 Y受体亚型（P2 Y（1）、P2 Y（2）和P2 Y（11））表达的证据，MDCK-D-1细胞是来自亲本MDCK的亚克隆。这些受体似乎与钙和蛋白激酶C活性的增加偶联，可能是通过Gq/G（11）介导的磷脂酶C.4的激活。此外，P2 Y受体激活可促进cAMP的显著增加。这包括P2 Y（2）受体介导的环加氧酶（考克斯）依赖性组分和由其他P2 Y受体介导的另一种COX非依赖性组分。我们已经证明，改变细胞生长的培养基会释放ATP，进而激活P2 Y受体。这种ATP的释放主要是为了提高这些细胞的基础cAMP水平。这些数据表明，MDCK细胞是一个有用的模型，以定义上皮细胞的细胞外核苷酸的调节。特别值得注意的是，ATP的自发或牵张诱导的释放以及随后一种或多种P2 Y受体的激活有助于建立信号传导途径的基础活性。
1. Madin-Darby canine kidney (MDCK) cells, a well-differentiated renal epithelial cell line derived from distal tubule/collecting duct, respond to extracellular nucleotides by altering ion flux and the production of arachidonic acid-derived products, in particular prostaglandin E-2 (PGE(2)). Our work has defined the receptors and signalling events involved in such responses.2. We have found evidence for expression of at least three P2Y receptor subtypes (P2Y(1), P2Y(2) and P2Y(11)) in MDCK-D-1 cells, a subclone from parental MDCK.3. These receptors appear to couple to increases in calcium and protein kinase C activity, probably via a Gq/G(11)-mediated activation of phospholipase C.4. In addition, P2Y receptor activation can promote a prominent increase in cAMP. This includes both a P2Y(2) receptor-mediated cyclo-oxygenase (COX)-dependent component and another COX-independent component mediated by other P2Y receptors.5. We have documented that changing media in which cells are grown releases ATP and, in turn, activates P2Y receptors. Such release of ATP contributes in a major way to basal cAMP levels in these cells.6. The data indicate that MDCK cells are a useful model to define the regulation of epithelial cells by extracellular nucleotides. Of particular note, spontaneous or stretch-induced release of ATP and subsequent activation of one or more P2Y receptors contributes to establishing the basal activity of signalling pathways.