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Por favor, use este identificador para citar o enlazar este documento: https://ria.asturias.es/RIA/handle/123456789/376
Título : Residue 826 in the Calcium-Sensing Receptor (CaR) is implicated in the
Autor : González Suárez, Ignacio
Fernández Martín, José L.
Rodríguez, Isabel
Santamaría, Iñigo
Coto García, Eliecer
Cannata Andía, Jorge B.
Palabras clave : PTH
Calcium-sensing receptor
Site-directed mutagenesis
Fecha de publicación : 2010
Editorial : Springer Verlag
Citación : Calcif tissue Int.2010;86:227-233
Resumen : Within the extracellular loops of the seven transmembrane domain of the calcium-sensing receptor (CaR) there is a region (I819-E837) relevant for calcimimetic activity. As the naturally occurring variant Ala826Thr is within this important region, it may be postulated that this change may influence the CaR response to calcium and R-568. Human embryonic kidney (HEK-293) cells transiently transfected with three different human CaR (wild type [A826], variant allele [T826] and artificial mutant [W826]) were used to test the ability of calcium alone or in combination with the calcimimetics R-568 to modulate CaR activity. CaR activation was detected by flow cytometry using a fluorescent probe. Intracellular calcium changes were measured in response to changes in extracellular calcium alone or with different R-568 concentrations. The change of the alanine in the 826 position (A826) for threonine (T826) worsened calcium sensitivity, increasing EC50 value from 2.34±0.48 mM (A826, wild type) to 2.96±0.75 mM (T826) (p<0.05). The T826 receptor reached similar response with 1 μM R-568 compared with the wild type receptor. On the contrary, the artificial introduction of a tryptophan in the same position (W826) did not affect calcium sensitivity (EC50= 2.64±0.81 mM) but reduced the ability of the receptor to respond to R-568. The results demonstrate the importance of the 826 residue in the CaR the response to calcium and calcimimetics. Since A826T change was described as a natural variant, the differences in calcium and calcimimetic response observed between both alleles could have potential clinical impact.
URI : https://ria.asturias.es/RIA/handle/123456789/376
ISSN : 1432-0827
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