Heteromerization of chemokine (C-X-C motif) receptor 4 with α1A/B-adrenergic receptors controls α1-adrenergic receptor function
Abstract
α1-Adrenergic receptors are important for the regulation of vascular function and are targeted clinically for blood pressure control. Here, we provide evidence that α1A/B-adrenergic receptors (AR) form heteromeric complexes with chemokine (C-X-C motif) receptor 4 (CXCR4) on the cell surface of vascular smooth muscle cells. We show that disruption of α1A/B-AR:CXCR4 heteromeric complexes inhibits α1-AR–mediated functions in vascular smooth muscle cells and that treatment with CXCR4 agonists enhances the potency of the α1-AR agonist phenylephrine to increase blood pressure. These findings extend the current understanding of the molecular mechanisms regulating α1-AR and provide an example of G protein-coupled receptor heteromerization with important functional implications. Compounds targeting the α1A/B-AR:CXCR4 interaction could provide an alternative pharmacological approach to modulating blood pressure.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 16, 2015
- Source ID
- 10.1073/pnas.1417564112
Entities
People
- Abhishek Tripathi
- Brian F Volkman
- Kenneth L. Byron
- Lioubov I. Brueggemann
- Matthias Majetschak
- Nadya I. Tarasova
- P. Geoff Vana
- Tanmay S. Chavan
- Vadim Gaponenko
Organizations
- American Heart Association
- Medical College of Wisconsin
- National Cancer Institute
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
- Stritch School of Medicine
- Telemedicine and Advanced Technology Research Center
- University of Illinois Urbana–Champaign