Extracellular calcium-sensing receptor: structural and functional features and association with diseases

Extracellular calcium-sensing receptor: structural and functional features and association with diseases

Autor Hauache, Omar Magid Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo The recently cloned extracellular calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays an essential role in the regulation of extracellular calcium homeostasis. This receptor is expressed in all tissues related to this control (parathyroid glands, thyroid C-cells, kidneys, intestine and bones) and also in tissues with apparently no role in the maintenance of extracellular calcium levels, such as brain, skin and pancreas. The CaR amino acid sequence is compatible with three major domains: a long and hydrophilic aminoterminal extracellular domain, where most of the activating and inactivating mutations described to date are located and where the dimerization process occurs, and the agonist-binding site is located, a hydrophobic transmembrane domain involved in the signal transduction mechanism from the extracellular domain to its respective G protein, and a carboxyterminal intracellular tail, with a well-established role for cell surface CaR expression and for signal transduction. CaR cloning was immediately followed by the association of genetic human diseases with inactivating and activating CaR mutations: familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are caused by CaR-inactivating mutations, whereas autosomal dominant hypoparathyroidism is secondary to CaR-activating mutations. Finally, we will comment on the development of drugs that modulate CaR function by either activating (calcimimetic drugs) or antagonizing it (calcilytic drugs), and on their 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.
Palavra-chave calcium-sensing receptor
familial hypocalciuric hypercalcemia
autosomal dominant hypoparathyroidism
calcimimetic drugs
calcilytic drugs
Idioma Inglês
Data de publicação 2001-05-01
Publicado em Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 34, n. 5, p. 577-584, 2001.
ISSN 0100-879X (Sherpa/Romeo, fator de impacto)
Publicador Associação Brasileira de Divulgação Científica
Extensão 577-584
Fonte http://dx.doi.org/10.1590/S0100-879X2001000500004
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000168735900004
SciELO S0100-879X2001000500004 (estatísticas na SciELO)
Endereço permanente http://repositorio.unifesp.br/handle/11600/1156

Exibir registro completo




Arquivo

Nome: S0100-879X2001000500004.pdf
Tamanho: 172.6KB
Formato: PDF
Descrição:
Abrir arquivo

Este item está nas seguintes coleções

Buscar


Navegar

Minha conta