Activation of EP1R by the hormone prostaglandin E2 (PGE2) causes airway smooth muscle cell constriction. In their current study, Liggett and colleagues found that PGE2 promotes the pairing or "dimerization" of EP1R with beta2AR, uncoupling b2AR from its signaling cascade, and reducing it's ability to cause muscle relaxation in response to beta2-AR–activating drugs. This may explain why in individuals with severe asthma whose PGE2 levels are elevated, some beta2-AR–-activating drugs are not effective.
In an accompanying commentary, Peter Barnes from Imperial College London reinforces how important the functional consequence of such receptor interactions can be. He muses about "the possibility of finding unexpected drug interactions or novel therapeutic agents that selectively activate certain heterodimer pairs" as well as the possibility of developing more selective drugs in the future for the treatment of asthma in individuals for whom current therapies have proven ineffective.
TITLE: Airway smooth muscle prostaglandin-EP1 receptors directly modulate beta2-adrenergic receptors within a unique heterodimeric complex
AUTHOR CONTACT:
Stephen B. Liggett
University of Maryland School of Medicine, Baltimore, Maryland, USA.
Phone: (410) 706-6256; Fax: (410) 706-6262; E-mail: sligg001@umaryland.edu .
View the PDF of this article at: https://www.the-jci.org/article.php?id=25840
ACCOMPANYING COMMENTARY
TITLE: Receptor heterodimerization: a new level of cross-talk
AUTHOR CONTACT:
Peter J. Barnes
National Heart and Lung Institute, Imperial College, London, United Kingdom.
Phone: 44-207-351-8174; Fax: 44-207-351-5675; E-mail: p.j.barnes@imperial.ac.uk .
View the PDF of this article at: https://www.the-jci.org/article.php?id=28535
Journal of Clinical Investigation