IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Histamine H2 overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling
Autor/es:
MONCZOR F, FERNANDEZ N, RIVEIRO E, MLADOVAN A, BALDI A, SHAYO C, DAVIO C
Revista:
BIOCHEMICAL PHARMACOLOGY
Referencias:
Año: 2006 vol. 71 p. 1219 - 1228
ISSN:
0006-2952
Resumen:
Knowing that cell-surface receptors that recognize and respond to extracellular stimuli are
key components for the regular communication between individual cells required for the
survival of any living organism, the aim of the present work was to investigate the effect of
H2R overexpression on the U937 signal transduction pathway and its consequences on cell
proliferation and differentiation. The overexpression ofH2R led to an increase in cAMP basal
levels, a leftward shift of agonist concentrationresponse curves, and similar maximal
response to agonist treatment, suggesting that overexpressed H2Rs act as functional spare
receptors. In this system cells triggered several mechanisms tending to restore cAMP basal
levels to those of the naı¨ve cells. H2R overexpression induced PDE activity stimulation and
GRK2 overexpression. In spite of the onset of these regulatory mechanisms, H2 agonist and
rolipram treatments induced the terminal differentiation of the H2R overexpressed clone,
conversely to the naı¨ve cells. Present findings show that stably H2R overexpression alters
cAMP signalling as the result of not only the amounts of second messenger generated but
also the activation or upregulation of various components of signalling cascade, leading to
an adapted biologically unique system. This adaptation may represent an advantage or a
disadvantage, depending on the biological system, but in any case, the existence of
compensatory mechanisms should be considered when a clinical treatment is designed.