Activation-Dependent Internalization of The Human Prostacyclin Receptor

  • Emer M. Smyth
  • Sandra C. Austin
  • Garret A. FitzGerald
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)


Prostacyclin (PGI2), the major cyclooxygenase-derived arachidonic acid metabolite formed in macrovascular endothelial cells’, is a potent vasodilator, an inhibitor of platelet aggregation2 and smooth muscle proliferation3 in vitro and an antithrombotic in mice4. Given the absence of PGI2 antagonists its role in the prevention of vascular disease in vivo has remained speculative.

The actions of PGI2 are transduced via IP, a G protein-coupled receptor (GPCR) which is coupled to activation of adenylyl cyclase (AC) and phospholipase C (PLC)5. GPCR are tightly regulated in response to agonist6. Rapid receptor phosphorylation, by second messenger kinases (PKC(s) and PKA) and/or GPCR kinases (GRKs) results in receptor-G-protein uncoupling and thus desensitization. Binding of an arrestin protein directs receptor internalization via clatharin-coated vesicles (CCVs). Many GPCR follow this pathway although several examples have been reported to diverge from this paradigm.


Green Fluorescent Protein Smooth Muscle Proliferation3 Coronary Artery Smooth Muscle Cell Prostacyclin Receptor Macrovascular Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Emer M. Smyth
    • 1
  • Sandra C. Austin
    • 1
  • Garret A. FitzGerald
    • 1
  1. 1.The Center for Experimental Therapeutics University of PennsylvaniaPhiladelphia

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