Subtype-specific intracellular trafficking of alpha(2)-adrenergic receptors

The three alpha(2)-adrenergic receptor subtypes (alpha(2a), alpha(2b), and alpha(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 alpha(2)-receptor subtypes to undergo agonist-mediated internalization. The alpha(2a)-receptor does not internalize after agonist treatment. In contrast, we observed that the alpha(2b)-receptor is able to undergo agonist-induced internalization and seems to follow the same endosomal pathway used by the beta(2)-adrenergic receptor, Attempts to examine internalization of the alpha(2c)-receptor were complicated by the fact that the majority of the alpha(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 alpha(2c)-receptor after prolonged agonist treatment. However, we observed no significant movement of alpha(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 alpha(2c)-receptors in the same way they process the alpha(2a) or alpha(2b) subtypes.