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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/F1291    most recent 90557.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Parisi, E. Articles by Valdivielso, J. M. PubMed PubMed Citation Articles by Parisi, E. Articles by Valdivielso, J. M.

N-methyl-D-aspartate receptors are expressed in rat parathyroid gland and regulate PTH secretion

¹Research Laboratory, ²Nephrology Department, and ⁴Biochemistry Department Hospital Universitari Arnau de Vilanova, IRBLLEIDA, Lleida, Spain; and ³Unidad de Investigación and Nephrology Department, Hospital Universitario Reina Sofia, Córdoba, Spain

Submitted 17 September 2008 ; accepted in final form 5 April 2009

N-methyl-D-aspartate receptors (NMDAR) are tetrameric amino acid receptors which act as membrane calcium channels. The presence of the receptor has been detected in the principal organs responsible for calcium homeostasis (kidney and bone), pointing to a possible role in mineral metabolism. In the present work, the presence of the receptor was determined in normal parathyroid glands (PTG) by real-time PCR, immunoprecipitation, and immunohistrochemistry. Healthy animals showed a decrease in blood parathyroid hormone (PTH) levels 15 min after the treatment with NMDA. This effect was also observed in animals with high levels of PTH-induced EDTA injection, but not in uremic animals with secondary hyperparathyroidism (2HPT). Normal rat PTG incubated in media with low calcium concentration (0.8 mM CaCl₂) showed a decrease in PTH release when NMDA was added to the media. This effect of NMDA was abolished when glands were coincubated with MK801 (a pharmacological blocker of the NMDA channel) or PD98059 (an inhibitor of the ERK-MAPK pathway). Glands obtained from animals with 2HPT showed no effect of NMDA in the in vitro release of PTH, together with a decrease in the expression of NMDAR1. In conclusion, NMDA receptor is present in PTG and is involved in the regulation of the PTH release. The mechanism by which NMDAR exerts its function is through the activation of the MAPK cascade. In uremic 2HPT animals the receptor expression is downregulated and the treatment with NMDA does not affect PTH secretion.

secondary hyperparathyroidism; ERK-MAPK