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oai:recercat.cat:10459.1/571762024-12-05T22:36:29Zcom_2072_3622col_2072_479130

2024-12-05T22:36:29Z urn:hdl:10459.1/57176 Sustained activation of renal N-methyl-D-aspartate receptors decreases vitamin D synthesis: a possible role for glutamate on the onset of secondary HPT Parisi Capdevila, Eva Bozic, Milica Ibarz Escuer, Mercedes Panizo García, Sara Valcheva, Petya Coll, Blai Fernández i Giráldez, Elvira Valdivielso Revilla, José Manuel Paratyroid hormone Mitogen- activated protein kinase Hyerparatyroidism N-methyl-D-aspartate (NMDA) receptors (NMDAR) are tetrameric amino acid receptors that act as membrane calcium channels. The presence of the receptor has been detected in the principal organs responsible for calcium homeostasis (kidney, bone, and parathyroid gland), pointing to a possible role in mineral metabolism. The aim of this study was to test the effect of NMDAR activation in the kidney and on 1,25(OH)2D3 synthesis. We determined the presence of NMDAR subunits in HK-2 (human kidney cells) cells and proved its functionality. NMDA treatment for 4 days induced a decrease in 1 -hydroxylase levels and 1,25(OH)2D3 synthesis through the activation of the MAPK/ERK pathway in HK-2 cells. In vivo administration of NMDA for 4 days also caused a decrease in blood 1,25(OH)2D3 levels in healthy animals and an increase in blood PTH levels. This increase in PTH induced a decrease in the urinary excretion of calcium and an increase in urinary excretion of phosphorous and sodium as well as in diuresis. Bone turnover markers also increased. Animals with 5/6 nephrectomy showed low levels of renal 1 -hydroxylase as well as high levels of renal glutamate compared with healthy animals. In conclusion, NMDAR activation in the kidney causes a decrease in 1,25(OH)2D3 synthesis, which induces an increase on PTH synthesis and release. In animals with chronic kidney disease, high renal levels of glutamate could be involved in the downregulation of 1 -hydroxylase expression. This work was supported by FIS PI09/0299, FIS PI07/0427, and REDINREN (16/06). 2024-12-05T22:36:29Z 2024-12-05T22:36:29Z 2016-06-09T08:29:39Z 2025-01-01 2010 article publishedVersion http://hdl.handle.net/10459.1/57176 Reproducció del document publicat a https://doi.org/10.1152/ajpendo.00428.2010 AJP- Endocrinology and Metabolism, 2010, vol. 299, núm. 5, p. E825-E831 (c) American Physiological Society, 2010 info:eu-repo/semantics/restrictedAccess American Physiological Society