Conserved transducer coupling but different effector linkage upon expression of the myeloid fMet-Leu-Phe receptor in insulin secreting cells.
AUTOR(ES)
Lang, J
RESUMO
In neutrophils fMet-Leu-Phe activates phospholipase C via a pertussis toxin sensitive G-protein and induces granule secretion. We have transfected a human cDNA sequence encoding the fMet-Leu-Phe receptor into the insulin secreting cell line RINm5F to study receptor-effector coupling with special regard to secretion. Stable overexpression resulted in membrane hyperpolarization, reduction of cAMP accumulation and inhibition of insulin secretion upon exposure of cells to fMet-Leu-Phe with EC50 values in the pmol range. As in the neutrophil, nanomolar concentrations of ligand induced membrane depolarization and activation of phospholipase C, with subsequent mobilization and influx of calcium. In permeabilized cells the inhibitory effect of fMet-Leu-Phe on secretion was partially retained indicating a direct action of the fMet-Leu-Phe receptor on exocytosis. Pertussis toxin abolished the effects of fMet-Leu-Phe. Our results suggest conserved coupling from fMet-Leu-Phe receptor to pertussis toxin sensitive transducers analogous to the mechanism in neutrophils. However, the net biological effect of receptor activation is determined by additional factors intrinsic to the host cell.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=413515Documentos Relacionados
- Cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Correlation to changes in the cytosolic free Ca2+ level and action of phorbol myristate acetate.
- Pertussis toxin inhibits fMet-Leu-Phe- but not phorbol ester-stimulated changes in rabbit neutrophils: role of G proteins in excitation response coupling.
- Association of the N-formyl-Met-Leu-Phe receptor in human neutrophils with a GTP-binding protein sensitive to pertussis toxin.
- Regulation of surface expression of the granulocyte/macrophage colony-stimulating factor receptor in normal human myeloid cells.
- Cloning and functional characterization of a third pituitary adenylate cyclase-activating polypeptide receptor subtype expressed in insulin-secreting cells.