Overexpression of beta -arrestin and beta -adrenergic receptor kinase augment desensitization of beta sub(2)-adrenergic receptors

• Published in: The Journal of biological chemistry 1993-01, Vol.268 (5), p.3201-3208
• Main Authors: Pippig, S, Andexinger, S, Daniel, K, Puzicha, M, Caron, M G, Lefkowitz, R J, Lohse, MJ
• Format: Article
• Language: English
• Subjects: adrenergic; beta -adrenergic receptor kinase; beta -arrestin; CHO cells; desensitization; expression; receptors
• ISSN: 0021-9258

Receptor-specific or homologous desensitization of beta sub(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 sub(2)-adrenergic receptors ( approximately equals 80 and approximately equals 600 fmol/mg of membrane protein). We studied the process of desensitization induced by the beta -adrenergic receptor agonist isoproterenol. In cells expressing high levels of beta sub(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 equals 50% in control cells, approximately equals 80% in beta ARK-overexpressing cells, and approximately equals 90% in beta -arrestin-overexpressing cells. In cells expressing low levels of beta sub(2)-adrenergic receptors, these values were approximately equals 50, approximately equals 60, and approximately equals 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.