Chronic effects of catecholamines on the beta 2-adrenoreceptor system in cultured human airway epithelial cells

The American Journal of Physiology
S G KelsenJ L Benovic

Abstract

Chronic catecholamine treatment induces beta-adrenergic receptor (beta AR) downregulation, i.e., a loss of total cell receptors. In the human respiratory tract, the mechanism(s) underlying beta AR downregulation remains poorly understood. The present study, therefore, examined the effects of 24 h of exposure to isoproterenol (Iso; 10 nM or 1 microM) on beta AR density and the rate of beta AR degradation, steady-state beta 2-adrenergic receptor (beta 2 AR) mRNA levels, and the content of Gs alpha and Gi alpha proteins in cultured human bronchial epithelial cells (i.e., the BEAS-2B cell line). beta AR density assessed by binding with [125I]iodopindolol decreased in a dose-dependent fashion with 24 h of Iso exposure. With Iso (1 microM), beta AR density decreased by approximately 82%. In contrast, forskolin (100 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM), agents that also increase adenosine 3',5'-cyclic monophosphate (cAMP) levels, had no significant effect on beta AR density. Iso exposure also elicited a concomitant decrease in Iso-stimulated cAMP but had no significant effect on the content of the G proteins G alpha i2 and Gs alpha assessed by immunoblotting and toxin-catalyzed ADP ribosylation. Of note, I...Continue Reading

Citations

Jan 25, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·D J RombergerT A Wyatt
Oct 13, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·M O AksoyS G Kelsen
Mar 7, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Eric E MorganMichael B Maron
May 25, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Steven G KelsenThomas J Rogers
Aug 30, 2003·American Journal of Respiratory and Critical Care Medicine·Yochai AdirJacob I Sznajder

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