Regulation of the cellular localization and signaling properties of the α(1B)- and α(1D)-adrenoceptors by agonists and inverse agonists

Dan F. McCune, Stephanie E. Edelmann, Jennifer R. Olges, Ginell R. Post, Bruce A. Waldrop, David J.J. Waugh, Dianne M. Perez, Michael T. Piascik

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


The regulation of the cellular distribution and intracellular signaling properties of the α(1B)- and α(1D)- adrenoceptor (α1-AR) subtypes was examined in stably transfected Rat 1 fibroblasts. In unstimulated cells, α(1B)-AR expression was noted primarily on the cell surface. Treatment with phenylephrine induced internalization of the α(1B)-AR and promoted association with arrestin 2. The internalized α(1B)-AR colocalized with the transferrin receptor, an endosomal marker. In unstimulated fibroblasts, the α(1D)-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 α(1D)-AR was redistributed from intracellular sites to the cellular periphery and was no longer associated with the transferrin receptor or arrestin 2. α(1D)-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 α(1B) -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 α(1B)-AR exhibits expected G protein-coupled receptor activity regarding cellular localization, agonist-mediated internalization, and coupling to second messengers; and 3) the α(1D)-AR is constitutively active and, as a result, is localized to intracellular compartments involved in receptor recycling.

Original languageEnglish
Pages (from-to)659-666
Number of pages8
JournalMolecular Pharmacology
Issue number4
StatePublished - 2000

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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