Role of cAMP and calcium influx in endothelin-1-induced ANP release in rat cardiomyocytes
Role of cAMP and calcium influx in endothelin-1-induced ANP release in rat cardiomyocytes
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DOI：
10.1152/ajpendo.1997.273.5.e922
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发表时间：
1997-11-01
影响因子：
5.1
通讯作者：
Lang, U
中科院分区：
文献类型：
--
作者：
Rebsamen, MC;Church, DJ;Lang, U
在新生大鼠心室心肌细胞中研究了内皮素-1 (ET-1) 诱导心房钠尿肽 (ANP) 释放的机制。这些细胞表达单一高亲和力类别的 ETA 受体（解离常数 = 54 +/- 18 pM，n = 3），但不表达 ETB 受体。心肌细胞与 ET-1 一起孵育导致浓度依赖性 ANP 释放和前列环素产生。 ET-1 诱导的 ANP 释放既不受蛋白激酶 C (PKC) 抑制或下调的影响，也不受环氧合酶抑制的影响，表明 ET-1 刺激的 ANP 分泌不是 PKC 介导的前列腺素依赖性过程。此外，ET-1 显着刺激 3',5'-环单磷酸腺苷 (cAMP) 的产生并增加这些制剂中的胞质钙浓度。 cAMP 拮抗剂 Rp-cAMPS（cAMP 的 Rp 非对映异构体）可减少 ET-1 诱导的钙内流和 ANP 释放。此外，在硝苯地平存在以及细胞外钙不存在的情况下，ET-1诱导的ANP分泌受到强烈抑制。因此，我们的结果表明，ET-1 通过 ETA 受体介导的途径刺激心室心肌细胞中的 ANP 释放，该途径涉及 cAMP 形成和硝苯地平敏感钙通道的激活。
The mechanism of endothelin-1 (ET-1)-induced atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. These cells expressed a single high-affinity class of ETA receptor (dissociation constant = 54 +/- 18 pM, n = 3), but no ETB receptors. Incubation of cardiomyocytes with ET-1 led to concentration-dependent ANP release and prostacyclin production. ET-1-induced ANP release was affected by neither protein kinase C (PKC) inhibition or downregulation nor by cyclooxygenase inhibition, indicating that ET-1-stimulated ANP secretion is not a PKC-mediated, prostaglandin-dependent process. Furthermore, ET-1 significantly stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production and increased cytosolic calcium concentration in these preparations. Both ET-1-induced calcium influx and ANP release were decreased by the cAMP antagonist Rp-cAMPS, the Rp diastereoisomer of cAMP. Moreover, ET-1-induced ANP secretion was strongly inhibited in the presence of nifedipine as well as in the absence of extracellular calcium. Thus our results suggest that ET-1 stimulates ANP release in ventricular cardiomyocytes via an ETA receptor-mediated pathway involving cAMP formation and activation of a nifedipine-sensitive calcium channel.