Dopamine fails to inhibit Na,H-exchanger in proximal tubules of obese Zucker rats.
Dopamine fails to inhibit Na,H-exchanger in proximal tubules of obese Zucker rats.
复制标题
多巴胺不能抑制肥胖 Zucker 大鼠近端肾小管中的 Na,H 交换器。
DOI：
10.1081/ceh-100107389
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Lokhandwala,MF
中科院分区：
文献类型：
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作者：
Hussain,T;Becker,M;Beheray,S;Lokhandwala,MF
多巴胺通过d1样受体的激活抑制Na， k - atp酶和Na， h -交换酶，随后增加钠的排泄。我们之前报道过多巴胺不能抑制肥胖Zucker大鼠近端小管（PTs）中的Na， k - atp酶。本研究旨在研究多巴胺对瘦型和肥胖型Zucker大鼠PTs中Na， h -交换剂的影响，并探讨d1样受体偶联信号转导通路介导Na， h -交换剂的抑制。我们发现，多巴胺在瘦大鼠的PTs中抑制Na， h -交换剂，但在肥胖大鼠中不存在这种反应。在刷状边界膜中，[3H]SCH 23390结合显示肥胖大鼠与瘦大鼠相比d1样受体结合位点减少了约45%。多巴胺刺激瘦大鼠PTs中cAMP的积累，但在肥胖大鼠中没有。福斯克林介导的cAMP刺激在瘦大鼠和肥胖大鼠中相似。与瘦鼠相比，肥胖大鼠的PTs中多巴胺以及福斯克林和二丁基camp介导的蛋白激酶A （PKA）刺激减少。这些数据提示，肥胖大鼠PTs中多巴胺无法抑制Na， h -交换剂的作用可能与d1样受体结合位点的减少、与信号通路的缺陷偶联以及PKA的无法激活有关。这种现象可能导致肥胖Zucker大鼠钠重吸收增加和高血压的发生。
Dopamine via the activation of D1-like receptors inhibits Na,K-ATPase and Na,H-exchanger and subsequently increases sodium excretion. We have previously reported that dopamine failed to inhibit Na,K-ATPase in the proximal tubules (PTs) of obese Zucker rats. The present study was designed to determine the effect of dopamine on Na,H-exchanger in PTs of lean and obese Zucker rats, and examine D1-like receptor-coupled signal transduction pathway mediating the inhibition of Na,H-exchanger. We found that dopamine inhibited Na,H-exchanger in the PTs of lean rats but this response was absent in obese rats. In brush border membranes, [3H]SCH 23390 binding revealed a, ∼45% reduction in D1-like receptor binding sites in obese compared to lean rats. Dopamine stimulated cAMP accumulation in PTs of lean but not in obese rats. Forskolin-mediated stimulation of cAMP was similar in lean and obese rats. Dopamine as well as forskolin and dibutyryl cAMP-mediated stimulation of protein kinase A (PKA) was reduced in PTs of obese compared to lean rats. The data suggest that reduction in D1-like receptor binding sites, defective coupling with signaling pathway and inability of PKA activation may be responsible for the failure of dopamine to inhibit Na,H-exchanger in PTs of obese rats. This phenomenon may contribute to an increase in sodium reabsorption and development of hypertension in obese Zucker rats.