Abstract
Receptor-specific or homologous desensitization of beta 2-adrenergic
receptors is thought to be effected via phosphorylation of the receptor
by the beta-adrenergic receptor kinase (beta ARK), followed by binding
of beta-arrestin. We have generated stably transfected Chinese hamster
ovary cell lines overexpressing either of the two regulatory proteins
and also expressing low or high levels of beta 2-adrenergic receptors
(approximately 80 and approximately 600 fmol/mg of membrane protein).
In these cells, we studied the process of desensitization induced
by the beta-adrenergic receptor agonist isoproterenol. In cells expressing
high levels of beta 2-adrenergic receptors, desensitization to high
concentrations of isoproterenol (previously shown to be mediated
by both beta ARK and protein kinase A) amounted to approximately
50% in control cells, approximately 80% in beta ARK-overexpressing
cells, and approximately 90% in beta-arrestin-overexpressing cells.
In cells expressing low levels of beta 2-adrenergic receptors, these
values were approximately 50, approximately 60, and approximately
60%, respectively. Desensitization to low concentrations of isoproterenol
(previously shown to be essentially protein kinase A-mediated and
not receptor-specific, i.e. heterologous) was not affected by overexpression
of either beta ARK or beta-arrestin. These data suggest that in cells
expressing high levels of beta 2-adrenergic receptors, beta-arrestin
and beta ARK become limiting for homologous receptor desensitization.
They provide further support for the involvement of these two proteins
in the regulation of beta 2-adrenergic receptor function.
Users
Please
log in to take part in the discussion (add own reviews or comments).