Signaling pathways involved in atrial natriuretic factor and dopamine regulation of renal Na+, K+-ATPase activity
Signaling pathways involved in atrial natriuretic factor and dopamine regulation of renal Na+, K+-ATPase activity
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DOI：
10.1016/j.regpep.2006.08.001
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发表时间：
2007-01-10
影响因子：
--
通讯作者：
Fernandez, Belisario E.
中科院分区：
文献类型：
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作者：
Correa, Alicia H.;Choi, Marcelo R.;Fernandez, Belisario E.
多巴胺(DA)和心钠素(ANF)具有共同的生理效应。我们假设ANF和肾脏多巴胺能系统可以相互作用，并增强多肽的利钠和利尿作用。我们以前曾报道，ANF刺激的肾小管细胞对DA的摄取是由利钠肽A受体(NPR-A)介导的。我们的目的是研究介导ANF对肾脏H-3-DA摄取的信号通路。亚甲蓝(10 AM)是鸟苷酸环化酶(GC)的非特异性抑制剂，可钝化ANF对DA摄取的增加。可溶性GC的特异性抑制剂ODQ(10 MU M)不能改变DA摄取，也不能逆转ANF诱导的DA摄取增加，因此必须放弃NO依赖途径的参与。第二个信使是cGMP，因为类似的125亩M8-BR-cGMP模拟ANF效应。蛋白激酶G(PKG)的特异性抑制剂KT 5823(1mU M)阻断了ANF的作用，表明PKG参与了ANF的作用。我们检测ANF对DA摄取的影响是否能够改变Na+，K+-三磷酸腺苷酶(Na+，K+-ATPase)的活性。实验采用卡比多巴抑制肾DA合成和诺米芬新阻断神经元DA摄取的方法。在这些条件下，肾脏的Na+，K+-ATPase活性增加，与DA利用率的降低一致。在相似条件下，加入外源DA后，随着DA利用率的恢复，酶活性有降低的趋势。单独加入ANF和DA对钠泵的作用相似，但当两者同时加入时，Na+，K+-ATPase活性降低。此外，神经元外摄取阻滞剂氢化可的松抑制了后一种效应。总之，ANF通过激活与GC偶联的NPR-A受体，并通过cGMP作为第二信使和PKG来传递信号，从而刺激外部皮质组织的神经元外DA摄取。多巴胺和心钠素可能通过一个共同的途径实现其作用，该途径涉及肾小管Na+，K+-ATPase的可逆失活。这一机制表明，DA-ANF关系参与了钠重吸收减少和钠尿增加的调节。(C)2006爱思唯尔B.V.保留所有权利。
Dopamine (DA) and atrial natriuretic factor (ANF) share a number of physiological effects. We hypothesized that ANF and the renal dopaminergic system could interact and enhance the natriuretic and diuretic effects of the peptide. We have previously reported that the ANF-stimulated DA uptake in renal tubular cells is mediated by the natriuretic peptide type-A receptor (NPR-A). Our aim was to investigate the signaling pathways that mediate ANF effects on renal H-3-DA uptake. Methylene blue (10 AM), an unspecific inhibitor of guanylate cyclase (GC), blunted ANF elicited increase of DA uptake. ODQ (10 mu M) a specific inhibitor of soluble GC, did not modify DA uptake and did not reverse ANF-induced increase of DA uptake; then the participation of nitric oxide-dependent pathways must be discarded. The second messenger was the cGMP since the analogous 125 mu M 8-Br-cGMP mimicked ANF effects. The specific inhibitor of the protein kinase G (PKG), KT 5823 (1 mu M) blocked ANF effects indicating that PKG is involved. We examined if ANF effects on DA uptake were able to modify Na+, K+-adenosine triphosphatase (Na+, K+-ATPase) activity. The experiments were designed by means of inhibition of renal DA synthesis by carbidopa and neuronal DA uptake blocked by nomifensine. In these conditions renal Na+, K+-ATPase activity was increased, in agreement with the decrease of DA availability. When in similar conditions, exogenous DA was added to the incubation medium, the activity of the enzyme tended to decrease, following to the restored availability of DA. The addition of ANF alone had similar effects to the addition of DA on the sodium pump, but when both were added together, the activity of Na+, K+-ATPase was decreased. Moreover, the extraneuronal uptake blocker, hydrocortisone, inhibited the latter effect. In conclusion, ANF stimulates extraneuronal DA uptake in external cortex tissues by activation of NPR-A receptors coupled to GC and it signals through cGMP as second messenger and PKG. Dopamine and ANF may achieve their effects through a common pathway that involves reversible deactivation of renal tubular Na+, K+-ATPase activity. This mechanism demonstrates a DA-ANF relationship involved in the modulation of both decreased sodium reabsorption and increased natriuresis. (c) 2006 Elsevier B.V. All rights reserved.