Subtype-Specific Intracellular Trafficking of α₂-Adrenergic Receptors

Abstract

The three α₂-adrenergic receptor subtypes (α_2a, α_2b, and α_2c) are highly homologous G protein-coupled receptors. These receptors all couple to pertussis toxin-sensitive G proteins and have relatively similar pharmacological properties. To further explore functional differences between these receptors, we used immunocytochemical techniques to compare the ability of the three α₂-receptor subtypes to undergo agonist-mediated internalization. The α_2a-receptor does not internalize after agonist treatment. In contrast, we observed that the α_2b-receptor is able to undergo agonist-induced internalization and seems to follow the same endosomal pathway used by the β₂-adrenergic receptor. Attempts to examine internalization of the α_2c-receptor were complicated by the fact that the majority of the α_2c-receptor resides in the endoplasmic reticulum and cis/medial Golgi and there is relatively little cell surface localization. Nevertheless, we were able to detect some internalization of the α_2c-receptor after prolonged agonist treatment. However, we observed no significant movement of α_2c-receptor from the intracellular pool to the plasma membrane during a 4-hr treatment of cells with cycloheximide, suggesting that these cells are unable to process α_2c-receptors in the same way they process the α_2a or α_2b subtypes.