TY - JOUR T1 - Regulation of the Cellular Localization and Signaling Properties of the α<sub>1B</sub>- and α<sub>1D</sub>-Adrenoceptors by Agonists and Inverse Agonists JF - Molecular Pharmacology JO - Mol Pharmacol SP - 659 LP - 666 DO - 10.1124/mol.57.4.659 VL - 57 IS - 4 AU - Dan F. McCune AU - Stephanie E. Edelmann AU - Jennifer R. Olges AU - Ginell R. Post AU - Bruce A. Waldrop AU - David J. J. Waugh AU - Dianne M. Perez AU - Michael T. Piascik Y1 - 2000/04/01 UR - http://molpharm.aspetjournals.org/content/57/4/659.abstract N2 - The regulation of the cellular distribution and intracellular signaling properties of the α1B- and α1D- adrenoceptor (α1-AR) subtypes was examined in stably transfected Rat 1 fibroblasts. In unstimulated cells, α1B-AR expression was noted primarily on the cell surface. Treatment with phenylephrine induced internalization of the α1B-AR and promoted association with arrestin 2. The internalized α1B-AR colocalized with the transferrin receptor, an endosomal marker. In unstimulated fibroblasts, the α1D-AR was detected in a perinuclear orientation and was colocalized with arrestin 2 in a compartment also containing the transferrin receptor. After treatment with prazosin, which exhibits inverse agonist properties, the α1D-AR was redistributed from intracellular sites to the cellular periphery and was no longer associated with the transferrin receptor or arrestin 2. α1D-AR-expressing cells exhibited a high degree of basal activity for both inositol phosphate formation and extracellular signal regulated kinase (ERK), which was reduced by treatment with prazosin. In these cells, phenylephrine induced a dose-dependent increase in inositol phosphate formation but had no effect on ERK activity. In α1B -AR-expressing cells, phenylephrine stimulated both inositol phosphate formation and ERK activity. These data show that: 1) there are differences in the cellular localization of the α1-AR subtypes; 2) the α1B-AR exhibits expected G protein-coupled receptor activity regarding cellular localization, agonist-mediated internalization, and coupling to second messengers; and 3) the α1D-AR is constitutively active and, as a result, is localized to intracellular compartments involved in receptor recycling. ER -