Effects of guanine, inosine, and xanthine nucleotides on beta(2)-adrenergic receptor/G(s) interactions: evidence for multiple receptor conformations.
Mol Pharmacol
; 56(2): 348-58, 1999 Aug.
Article
em En
| MEDLINE
| ID: mdl-10419554
ABSTRACT
The aim of our study was to examine the effects of different purine nucleotides [GTP, ITP, and xanthosine 5'-triphosphate (XTP)] on receptor/G protein coupling. As a model system, we used a fusion protein of the beta(2)-adrenergic receptor and the alpha subunit of the G protein G(s). GTP was more potent and efficient than ITP and XTP at inhibiting ternary complex formation and supporting adenylyl cyclase (AC) activation. We also studied the effects of several beta(2)-adrenergic receptor ligands on nucleotide hydrolysis and on AC activity in the presence of GTP, ITP, and XTP. The efficacy of agonists at promoting GTP hydrolysis correlated well with the efficacy of agonists for stimulating AC in the presence of GTP. This was, however, not the case for ITP hydrolysis and AC activity in the presence of ITP. The efficacy of ligands at stimulating AC in the presence of XTP differed considerably from the efficacies of ligands in the presence of GTP and ITP, and there was no evidence for receptor-regulated XTP hydrolysis. Our findings support the concept of multiple ligand-specific receptor conformations and demonstrate the usefulness of purine nucleotides as tools to study conformational states of receptors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nucleotídeos de Purina
/
Receptores Adrenérgicos beta 2
/
Subunidades alfa Gs de Proteínas de Ligação ao GTP
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Pharmacol
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos