Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Pharmacology ; 83(2): 88-94, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19065062

RESUMO

Protons act as neuromodulators and produce significant effects on synaptic transmission. The molecular basis of neuromodulation by extracellular protons is partially explained by their effects on certain neurotransmitter receptors and ion channels. The metabotropic glutamate receptors (mGluRs) are a family of eight receptor subtypes that are widely expressed throughout the mammalian CNS. In this study, the effects of physiologically relevant changes in extracellular pH were examined in mammalian cells expressing the mGluR subtypes: human mGluR1a, mGluR4a, mGluR5d or mGluR8b. The signal transduction coupling properties of mGluR4a and mGluR8b were switched from the adenylate cyclase (G(i)) pathway to the phospholipase C (G(q)) pathway by coexpression of a promiscuous G protein. Fluorometric imaging plate reader was used to measure changes in cytoplasmic calcium concentrations in response to agonist. Extracellular acidification from pH 8.0 to pH 6.5 progressively diminished mGluR4 responsiveness to the agonists L-glutamate and (2S,1'S,2'R)-2-(carboxycyclopropyl)glycine (L-CCG-I), and this inhibition was characterized by insurmountable antagonism. By comparison, extracellular acidification did not significantly alter mGluR8 responses to agonists. Furthermore, agonist activation of mGluR1a and mGluR5d was virtually unaffected by changes in pH. Because mGluR4 is expressed presynaptically and its activation inhibits the release of neurotransmitters such as glutamate and GABA, we propose that the net effect of proton inhibition of mGluR4 would be to reverse or prevent that suppression of neurotransmitter release. As such, local decreases in pH could have significant effects on the regulation of transmitter release and synaptic tone via modulation of mGluR4.


Assuntos
Concentração de Íons de Hidrogênio/efeitos dos fármacos , Prótons , Receptores de Glutamato Metabotrópico/metabolismo , Adenilil Ciclases/metabolismo , Regulação Alostérica/efeitos dos fármacos , Aminoácidos Dicarboxílicos/agonistas , Animais , Cálcio/agonistas , Cálcio/metabolismo , Cálcio/farmacologia , Linhagem Celular , Células Cultivadas , Líquido Extracelular/metabolismo , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Humanos , Líquido Intracelular/metabolismo , Neurotransmissores/metabolismo , Neurotransmissores/farmacologia , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Fosfolipases Tipo C/metabolismo , Xenopus , Ácido gama-Aminobutírico/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa