Mutações do Gene do Receptor Sensível ao Cálcio Extracelular e Suas Doenças Associadas

• Autor(a) principal: Miyashiro, Kozue [UNIFESP]
• Data de Publicação: 2002
• Outros Autores: Hauache, Omar M. [UNIFESP]
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1590/S0004-27302002000400012; http://repositorio.unifesp.br/handle/11600/1492
• topic: Calcium-sensing receptor; Familial hypocalciuric hypercalcemia; Neonatal severe hyperparathyroidism; Autosomal dominant hypoparathyroidism; Receptor sensível ao cálcio extracelular; Hipercalcemia hipocalciúrica familiar; Hiperparatiroidismo neonatal severo; Hipocalcemia autossômica dominante

The extracellular calcium-sensing receptor (CaR) is a G protein coupled receptor (GPCR) that plays a key role in the regulation of extracellular calcium homeostasis, being expressed in all tissues related to this control (parathyroid glands, thyroid C-cells, kidneys, intestine and bones). The cloning of the CaR was immediately followed by the association of genetic human diseases with inactivating and activating mutations of the CaR gene: familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT) are caused by inactivating mutations of the CaR gene, whereas autosomal dominant hypoparathyroidism is secondary to activating mutations of the CaR gene. In spite of being rare, these diseases should be considered in the differential diagnosis of hypercalcemic and hypocalcemic disorders. Recognition of the important role of the CaR for the regulation of extracellular calcium homeostasis motivated the development of drugs that modulate the CaR function, by either activating (calcimimetic drugs) or antagonizing it (calcilytic drugs). These drugs have potential therapeutic implications, such as medical control of specific cases of primary and uremic hyperparathyroidism with calcimimetic drugs and a potential treatment for osteoporosis with a calcilytic drug.