Activation-Dependent Internalization of The Human Prostacyclin Receptor
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.
KeywordsGreen Fluorescent Protein Smooth Muscle Proliferation3 Coronary Artery Smooth Muscle Cell Prostacyclin Receptor Macrovascular Endothelial Cell
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