Cytoskeleton-dependent endocytosis is required for apical type 1 angiotensin II receptor-mediated phospholipase C activation in cultured rat proximal tubule cells.
Cytoskeleton-dependent endocytosis is required for apical type 1 angiotensin II receptor-mediated phospholipase C activation in cultured rat proximal tubule cells.
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在培养的大鼠近曲小管细胞中，顶端 1 型血管紧张素 II 受体介导的磷脂酶 C 激活需要细胞骨架依赖性内吞作用。
DOI：
10.1172/jci116139
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Linas,SL
中科院分区：
文献类型：
--
作者：
Schelling,JR;Hanson,AS;Marzec,R;Linas,SL
肾近端小管钠重吸收可通过根尖或基底侧血管紧张素II （AII）增强。虽然AII在其他组织中激活磷脂酶C (PLC)，但AII在近端小管细胞的顶端或底外侧表面与PLC的偶联尚不清楚。为了确定AII是否导致PLC激活，以及顶端和基底外侧AII受体功能的差异，在可渗透的胶原包被支架上培养的大鼠近端小管细胞中，受体被单侧激活。顶端AII孵育导致浓度和时间依赖的三磷酸肌醇（IP3）形成。基底外侧AII引起更大的IP3反应。DuP 753可抑制AII诱导的顶端IP3生成，提示AII受体亚型1介导近端小管PLC激活。由于AII诱导的PLC激活发生在基底外侧AII受体被Sar-Leu AII或DuP 753占据时，因此，顶端AII信号不是由细胞旁配体泄漏到基底外侧受体引起的。苯基larsine oxide抑制内吞作用可以阻止aii诱导的顶端（而不是基底外侧）IP3的形成。秋水仙碱或细胞松弛素D破坏细胞骨架也能阻止aii诱导的IP3的产生。这些结果表明，在培养的大鼠近端小管细胞中，AII通过1型AII受体与PLC偶联，并且AII受体介导的PLC激活需要细胞骨架依赖的内噬作用。图片
Renal proximal tubule sodium reabsorption is enhanced by apical or basolateral angiotensin II (AII). Although AII activates phospholipase C (PLC) in other tissues, AII coupling to PLC on either apical or basolateral surfaces of proximal tubule cells is unclear. To determine if AII causes PLC activation, and the differences between apical and basolateral AII receptor function, receptors were unilaterally activated in rat proximal tubule cells cultured on permeable, collagen-coated supports. Apical AII incubation resulted in concentration- and time-dependent inositol trisphosphate (IP3) formation. Basolateral AII caused greater IP3 responses. Apical AII-induced IP3 generation was inhibited by DuP 753, suggesting that the type 1 AII receptor subtype mediated proximal tubule PLC activation. Apical AII signaling did not result from paracellular ligand leak to basolateral receptors since AII-induced PLC activation occurred when basolateral AII receptors were occupied by Sar-Leu AII or DuP 753. Inhibition of endocytosis with phenylarsine oxide prevented apical (but not basolateral) AII-induced IP3 formation. Cytoskeletal disruption with colchicine or cytochalasin D also prevented apical AII-induced IP3 generation. These results demonstrate that in cultured rat proximal tubule cells, AII is coupled to PLC via type 1 AII receptors and cytoskeleton-dependent endocytosis is required for apical (but not basolateral) AII receptor-mediated PLC activation.Images