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2-Adrenergic Receptors
Department of Molecular and Cellular Physiology, Stanford
University, Stanford, California 94305 (D.A.D., C.H.),
Institut
für Pharmakologie, Universität Würzburg, 97078 Würzburg, Germany (L.H.),
Department of Pharmacology and Clinical
Pharmacology, MediCity Research Laboratory, University of Turku,
FIN-20520 Turku, Finland (J.K.),
Biological Sciences, Stanford
University, Stanford, California 94305 (F.F.), and
Department of
Molecular and Cellular Physiology, Howard Hughes Medical Institute, and
Division of Cardiovascular Medicine, Stanford University, Stanford,
California 94305 (B.K.K.)
The three 
2-adrenergic receptor subtypes
(2a, 2b, and 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
2-receptor subtypes to undergo agonist-mediated
internalization. The 2a-receptor does not internalize
after agonist treatment. In contrast, we observed that the
2b-receptor is able to undergo agonist-induced internalization and seems to follow the same endosomal pathway used by
the 
2-adrenergic receptor. Attempts to examine
internalization of the 2c-receptor were complicated by
the fact that the majority of the 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 2c-receptor after prolonged
agonist treatment. However, we observed no significant movement of
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 2c-receptors in the same way they process the
2a or 2b subtypes.
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