ArticleBioscience reports2024
Co-localization of the sodium-glucose co-transporter-2 channel (SGLT-2) with endothelin ETA and ETB receptors in human cardiorenal tissue.
Article in Bioscience reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy and safety of endothelin receptor antagonists in non-diabetic kidney nephropathy : A systematic review and meta-analysis.Wiener klinische Wochenschrift · 2025Pooled it
- Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment.Cancer management and research · 2025Review
- Mangiferin mitigates dexamethasone-induced insulin resistance in rats: insight into vascular dysfunction and hepatic steatosis.Frontiers in pharmacology · 2025Article
- Localization of the therapeutic targets for endothelin receptor antagonists and sodium-glucose co-transporter 2 inhibitors in the chronic liver disease, primary sclerosing cholangitis.Frontiers in pharmacology · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
Endothelin (ET) receptor antagonists are being investigated in combination with sodium-glucose co-transporter-2 inhibitors (SGLT-2i). These drugs primarily inhibit the SGLT-2 transporter that, in humans, is thought to be mainly restricted to the renal proximal convoluted tubule, resulting in increased glucose excretion favouring improved glycaemic control and diuresis. This action reduces fluid retention with ET receptor antagonists. Studies have suggested SGLT-2 may also be expressed in cardiomyocytes of human heart. To understand the potential of combining the two classes of drugs, our aim was to compare the distribution of ET receptor sub-types in human kidney, with SGLT-2. Secondly, using the same experimental conditions, we determined if SGLT-2 expression could be detected in human heart and whether the transporter co-localised with ET receptors.
methodsImmunocytochemistry localised SGLT-2, ETA and ETB receptors in sections of histologically normal kidney, left ventricle from patients undergoing heart transplantation or controls. Primary antisera were visualised using fluorescent microscopy. Image analysis was used to measure intensity compared with background in adjacent control sections.
resultsAs expected, SGLT-2 localised to epithelial cells of the proximal convoluted tubules, and co-localised with both ET receptor sub-types. Similarly, ETA receptors predominated in cardiomyocytes; low (compared with kidney but above background) positive staining was also detected for SGLT-2. DISCUSSION: Whether low levels of SGLT-2 have a (patho)physiological role in cardiomyocytes is not known but results suggest the effect of direct blockade of sodium (and glucose) influx via SGLT-2 inhibition in cardiomyocytes should be explored, with potential for additive effects with ETA antagonists.
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