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. The se receptors all couple to pertussis toxin sensitive G proteins and ha ve relatively similar pharmacological properties. To further explore f unctional differences between these receptors, we used immunocytochemi cal techniques to compare the ability of the three alpha(2)-receptor s ubtypes to undergo agonist-mediated internalization. The alpha(2a)-rec eptor does not internalize after agonist treatment. In contrast, we ob served 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 majori ty of the alpha(2c)-receptor resides in the endoplasmic reticulum and cis/medial Golgi and there is relatively little cell surface localizat ion. Nevertheless, we were able to detect some internalization of the alpha(2c)-receptor after prolonged agonist treatment. However, we obse rved no significant movement of alpha(2c)-receptor from the intracellu lar 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.