Gastrin decreases Na+,K+-ATPase activity via a PI 3-kinase- and PKC-dependent pathway in human renal proximal tubule cells

American Journal of Physiology. Endocrinology and Metabolism
Tianbing LiuPedro A Jose

Abstract

The natriuretic effect of gastrin suggests a role in the coordinated regulation of sodium balance by the gastrointestinal tract and the kidney. The renal molecular targets and signal transduction pathways for such an effect of gastrin are largely unknown. Recently, we reported that gastrin induces NHE3 phosphorylation and internalization via phosphatidylinositol (PI) 3-kinase and PKCα. In this study, we show that gastrin induced the phosphorylation of human Na(+),K(+)-ATPase at serine 16, resulting in its endocytosis via Rab5 and Rab7 endosomes. The gastrin-stimulated phosphorylation of Na(+),K(+)-ATPase was dependent on PI 3-kinase because the phosphorylation was blocked by the PI 3-kinase inhibitor wortmannin. The phosphorylation of Na(+),K(+)-ATPase was also blocked by chelerythrine, a pan-PKC inhibitor, Gö-6976, a conventional PKC (cPKC) inhibitor, and BAPTA-AM, an intracellular calcium chelator, suggesting the importance of cPKC and intracellular calcium in the gastrin signaling pathway. The gastrin-mediated phosphorylation of Na(+),K(+)-ATPase was also inhibited by U-73122, a phospholipase C (PLC) inhibitor. These results suggest that gastrin regulates sodium hydrogen exchanger and pump in renal proximal tubule cells at t...Continue Reading

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Citations

Feb 9, 2016·Experimental Physiology·Pedro A JoseRobin A Felder
Jun 18, 2016·Frontiers in Physiology·Paula F KinoshitaCristoforo Scavone
Oct 27, 2016·American Journal of Physiology. Endocrinology and Metabolism·Xiaoliang JiangZhiwei Yang
Mar 8, 2017·Journal of the American Heart Association·Jian YangChunyu Zeng
Apr 6, 2016·Hypertension·Pedro A JoseGilbert M Eisner
Mar 5, 2020·Nature Reviews. Nephrology·Eric H J VerschurenJoost G J Hoenderop
Mar 30, 2017·Current Hypertension Reports·Shiqiang XiongZhiming Zhu
Jun 27, 2019·Current Hypertension Reports·Masami Tanaka, Hiroshi Itoh
Mar 17, 2017·American Journal of Physiology. Renal Physiology·Hiromi Takahashi-IwanagaToshihiko Iwanaga
May 1, 2021·International Journal of Molecular Sciences·Caini FanPrasad R Konkalmatt

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