ArticleEndocrinology2013
Gastrin induces sodium-hydrogen exchanger 3 phosphorylation and mTOR activation via a phosphoinositide 3-kinase-/protein kinase C-dependent but AKT-independent pathway in renal proximal tubule cells derived from a normotensive male human.
Article in Endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Increased oral sodium chloride intake in humans amplifies selectively postprandial GLP-1 but not GIP, CCK, and gastrin in plasma.Physiological reports · 2020Trial
- The Effect of Salt Intake and Potassium Supplementation on Serum Gastrin Levels in Chinese Adults: A Randomized Trial.Nutrients · 2017Trial
- Intestinal Gastrin/CCKBR Axis Protects against Type 2 Diabetes by Reducing Intestinal Glucose Absorption through the PI3K/Akt/eIF4B Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The GLP-1-mediated gut-kidney cross talk in humans: mechanistic insight.American journal of physiology. Cell physiology · 2024Review
- Regulation of the intestinal NaAmerican journal of physiology. Cell physiology · 2024Article
- Inhibition of protein kinase C-α and activation of ezrin byAmerican journal of physiology. Endocrinology and metabolism · 2023Article
- Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal NaHypertension (Dallas, Tex. : 1979) · 2022Article
- Metformin Inhibits NaFrontiers in physiology · 2022Article
- NFAT5 Is Involved in GRP-Enhanced Secretion of GLP-1 by Sodium.International journal of molecular sciences · 2021Article
- Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer.International journal of nanomedicine · 2021Article
- Stomach gastrin is regulated by sodium via PPAR-α and dopamine D1 receptor.Journal of molecular endocrinology · 2020Article
- Gastrin Attenuates Renal Ischemia/Reperfusion Injury by a PI3K/Akt/Bad-Mediated Anti-apoptosis Signaling.Frontiers in pharmacology · 2020Review
- Hypertension as a Metabolic Disorder and the Novel Role of the Gut.Current hypertension reports · 2019Review
- Exposure to Maternal Diabetes Mellitus Causes Renal Dopamine DHypertension (Dallas, Tex. : 1979) · 2018Article
- Gastrointestinal-Renal Axis: Role in the Regulation of Blood Pressure.Journal of the American Heart Association · 2017Review
- Phosphorylation and subcellular localization of NaJournal of physiology and biochemistry · 2017Article
- Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.American journal of physiology. Endocrinology and metabolism · 2017Article
- Gastrorenal Axis.Hypertension (Dallas, Tex. : 1979) · 2016Review
- The importance of the gastrorenal axis in the control of body sodium homeostasis.Experimental physiology · 2016Review
- 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 · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Gastrin is natriuretic, but its renal molecular targets and signal transduction pathways are not fully known. In this study, we confirmed the existence of CCKBR (a gastrin receptor) in male human renal proximal tubule cells and discovered that gastrin induced S6 phosphorylation, a downstream component of the phosphatidylinositol 3 kinase (PI3 kinase)-mammalian target of rapamycin pathway. Gastrin also increased the phosphorylation of sodium-hydrogen exchanger 3 (NHE3) at serine 552, caused its internalization, and decreased its expression at the cell surface and NHE activity. The phosphorylation of NHE3 and S6 was dependent on PI3 kinases because it was blocked by 2 different PI3-kinase inhibitors, wortmannin and LY294,002. The phosphorylation of NHE3 and S6 was not affected by the protein kinase A inhibitor H-89 but was blocked by a pan-PKC (chelerythrine) and a conventional PKC (cPKC) inhibitor (Gö6976) (10 μM) and an intracellular calcium chelator, 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester, suggesting the importance of cPKC and intracellular calcium in the gastrin signaling pathway. The cPKC involved was probably PKCα because it was phosphorylated by gastrin. The gastrin-mediated phosphorylation of NHE3, S6, and PKCα was via phospholipase C because it was blocked by a phospholipase C inhibitor, U73122 (10 μM). The phosphorylation (activation) of AKT, which is usually upstream of mammalian target of rapamycin in the classic PI3 kinase-AKT-p70S6K signaling pathway, was not affected, suggesting that the gastrin-induced phosphorylation of NHE3 and S6 is dependent on both PI3 kinase and PKCα but not AKT.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.