Milano Serena, Carmosino Monica, Gerbino Andrea, Saponara Ilenia, Lapi Dominga, Dal Monte Massimo, Bagnoli Paola, Svelto Maria, Procino Giuseppe
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
Department of Sciences, University of Basilicata, Potenza, Italy.
Front Physiol. 2021 Aug 13;12:695824. doi: 10.3389/fphys.2021.695824. eCollection 2021.
We previously showed that the beta-3 adrenergic receptor (BAR3) is expressed in most segments of the nephron where its agonism promotes a potent antidiuretic effect. We localized BAR3 in distal convoluted tubule (DCT) cells expressing the thiazide-sensitive sodium-chloride cotransporter (NCC). Aim of this study is to investigate the possible functional role of BAR3 on NCC modulation in DCT cells. Here, we found that, in mice, the knockout of BAR3 was paralleled by a significant attenuation of NCC phosphorylation, paralleled by reduced expression and activation of STE-20/SPS1-related proline-alanine-rich kinase (SPAK) and WNKs the main kinases involved in NCC activation. Conversely, in BAR1/2 knockout mice, we found reduced NCC abundance with no changes in the phosphorylation state of NCC. Moreover, selective BAR3 agonism promotes both SPAK and NCC activation in wild-type mouse kidney slices. In conclusion, our findings suggest a novel role for BAR3 in the regulation of NCC in DCT.
我们之前表明，β-3肾上腺素能受体（BAR3）在肾单位的大多数节段中表达，其激动作用可促进强大的抗利尿作用。我们将BAR3定位在表达噻嗪类敏感的氯化钠共转运体（NCC）的远曲小管（DCT）细胞中。本研究的目的是探讨BAR3对DCT细胞中NCC调节的可能功能作用。在此，我们发现，在小鼠中，BAR3基因敲除与NCC磷酸化的显著减弱同时出现，同时参与NCC激活的主要激酶STE-20/SPS1相关富含脯氨酸-丙氨酸激酶（SPAK）和WNKs的表达及激活减少。相反，在BAR1/2基因敲除小鼠中，我们发现NCC丰度降低，但NCC的磷酸化状态没有变化。此外，选择性BAR3激动作用可促进野生型小鼠肾切片中SPAK和NCC的激活。总之，我们的研究结果表明BAR3在DCT中NCC的调节中具有新的作用。
