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首页> 外文期刊>American Journal of Physiology >cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells.
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cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells.

机译：cAMP刺激肾脏收集导管A插入的细胞中的顶端V-ATPase积累，微绒毛伸长和质子挤出。

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摘要

Kidney proton-secreting A-intercalated cells (A-IC) respond to systemic acidosis by accumulating the vacuolar ATPase (V-ATPase) in their apical membrane and by increasing the length and number of apical microvilli. We show here that the cell-permeant cAMP analog CPT-cAMP, infused in vivo, results in an almost twofold increase in apical V-ATPase accumulation in AE1-positive A-IC within 15 min and that these cells develop an extensive array of apical microvilli compared with controls. In contrast, no significant change in V-ATPase distribution could be detected by immunocytochemistry in B-intercalated cells at the acute time point examined. To show a direct effect of cAMP on A-IC, we prepared cell suspensions from the medulla of transgenic mice expressing EGFP in IC (driven by the B1-subunit promoter of the V-ATPase) and exposed them to cAMP analogs in vitro. Three-dimensional reconstructions of confocal images revealed that cAMP induced a time-dependent growth of apical microvilli, starting within minutes after addition. This effect was blocked by the PKA inhibitor myristoylated PKI. These morphological changes were paralleled by increased cAMP-mediated proton extrusion (pHi recovery) by A-IC in outer medullary collecting ducts measured using the ratiometric probe BCECF. These results, and our prior data showing that the bicarbonate-stimulated soluble adenylyl cyclase (sAC) is highly expressed in kidney intercalated cells, support the idea that cAMP generated either by sAC, or by activation of other signaling pathways, is part of the signal transduction mechanism involved in acid-base sensing and V-ATPase membrane trafficking in kidney intercalated cells.
机译：肾质子分泌性A插入细胞（A-IC）对系统性酸中毒作出反应，方法是在其顶膜中积聚液泡ATPase（V-ATPase），并增加其顶端微绒毛的长度和数量。我们在这里显示，体内注入的可渗透细胞的cAMP类似物CPT-cAMP在15分钟内导致AE1阳性A-IC的根尖V-ATPase积累几乎增加了两倍，并且这些细胞形成了广泛的根尖阵列微绒毛与对照相比。相比之下，在所检查的急性时间点，B夹层细胞中的免疫细胞化学检测不到V-ATPase分布的显着变化。为了显示cAMP对A-IC的直接作用，我们从在IC中表达EGFP的转基因小鼠的髓质中制备了细胞悬液（由V-ATPase的B1亚基启动子驱动），并将其在体外暴露于cAMP类似物。共聚焦图像的三维重建显示，cAMP诱导了根尖微绒毛的时间依赖性生长，从添加后数分钟开始。该作用被PKA抑制剂肉豆蔻酰化的PKI阻断。这些形态学变化与使用比例探针BCECF测量的外髓质收集管中的A-IC增加了cAMP介导的质子挤出（pHi恢复）相平行。这些结果以及我们的先前数据表明，碳酸氢盐刺激的可溶性腺苷酸环化酶（sAC）在肾插层细胞中高表达，支持这样的观点，即由sAC或通过其他信号通路的激活产生的cAMP是信号的一部分肾脏插层细胞中涉及酸碱感测和V-ATPase膜运输的转导机制。

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