Sustained activation of renal N-methyl-D-aspartate receptors decreases vitamin D synthesis: a possible role for glutamate on the onset of secondary HPT
Loading...
Date
2010
Authors
Parisi Capdevila, Eva
Bozić Stanojević, Milica
Ibarz Escuer, Mercedes
Panizo García, Sara
Valcheva, Petya
Coll, Blai
Fernández i Giráldez, Elvira
Valdivielso Revilla, José Manuel
Other authors
Impact
Export
Share
Journal Title
Journal ISSN
Volume Title
Abstract
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.
Citation
Journal or Serie
AJP- Endocrinology and Metabolism, 2010, vol. 299, núm. 5, p. E825-E831