Pediatric Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Am J Physiol Renal Physiol. 2010 Jul;299(1):F49-54. doi: 10.1152/ajprenal.00582.2009. Epub 2010 May 12.
Prolactin is a natriuretic hormone and acts by inhibiting the activity of renal tubular Na(+)-K(+)-ATPase activity. These effects require an intact renal dopamine system. Here, we have studied by which mechanism prolactin and dopamine interact in Sprague-Dawley rat renal tissue. Na(+)-K(+)-ATPase activity was measured as ouabain-sensitive ATP hydrolysis in microdissected renal proximal tubular segments. Intracellular signaling pathways were studied by a variety of different techniques, including Western blotting using phosphospecific antibodies, immunoprecipitation, and biotinylation assays. We found that dopamine and prolactin regulated Na(+)-K(+)-ATPase activity via similar signaling pathways, including protein kinase A, protein kinase C, and phosphoinositide 3-kinase activation. The cross talk between prolactin and dopamine 1-like receptors was explained by a heterologous recruitment of dopamine 1-like receptors to the plasma membrane in renal proximal tubular cells. Prolactin had no effect on Na(+)-K(+)-ATPase activity in spontaneously hypertensive rats, a rat strain with a blunted response to dopamine. These results further emphasize the central role of the renal dopamine system in the interactive regulation of renal tubular salt balance.
催乳素是一种利钠激素，通过抑制肾管状 Na(+)-K(+)-ATPase 活性来发挥作用。这些作用需要完整的肾多巴胺系统。在这里，我们研究了催乳素和多巴胺在 Sprague-Dawley 大鼠肾组织中是如何相互作用的。通过测量微切割肾近端管状段对哇巴因敏感的 ATP 水解来测量 Na(+)-K(+)-ATPase 活性。通过多种不同的技术研究了细胞内信号通路，包括使用磷酸化特异性抗体的 Western blot 分析、免疫沉淀和生物素化测定。我们发现多巴胺和催乳素通过类似的信号通路调节 Na(+)-K(+)-ATPase 活性，包括蛋白激酶 A、蛋白激酶 C 和磷酸肌醇 3-激酶的激活。催乳素和多巴胺 1 样受体之间的串扰可以通过多巴胺 1 样受体在肾近端管状细胞中的质膜上的异源募集来解释。催乳素对自发性高血压大鼠（一种对多巴胺反应迟钝的大鼠品系）的 Na(+)-K(+)-ATPase 活性没有影响。这些结果进一步强调了肾多巴胺系统在肾小管盐平衡的相互调节中的核心作用。
