2026-04-13T07:36:25Zhttps://recercat.cat/oai/request

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

00925njm 22002777a 4500 dc Parisi Capdevila, Eva author Bozic, Milica author Ibarz Escuer, Mercedes author Panizo García, Sara author Valcheva, Petya author Coll, Blai author Fernández i Giráldez, Elvira author Valdivielso Revilla, José Manuel author 2016-06-09T08:29:39Z 2025-01-01 2010 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). http://hdl.handle.net/10459.1/57176 Paratyroid hormone Mitogen- activated protein kinase Hyerparatyroidism Sustained activation of renal N-methyl-D-aspartate receptors decreases vitamin D synthesis: a possible role for glutamate on the onset of secondary HPT