Prostacyclin - Mode of Action

Mode of Action

Prostacyclin effect Mechanism Cellular response
Classical
functions		 Vessel tone ↑cAMP, ↓ET-1
↓Ca2+, ↑K+		 ↓SMC proliferation
↑Vasodilation
Antiproliferative ↑cAMP
&earr;PPAR		 ↓Fibroblast growth
↑Apoptosis
Antithrombotic ↓Thromboxane-A2
↓PDGF		 ↓Platelet aggregation
↓Platelet adherence to vessel wall
Novel
functions		 Antiinflammatory ↓IL-1, IL-6
↑IL-10		 ↓Proinflammatory cytokines
↑Antiinflammatory cytokines
Antimitogenic ↓VEGF
↓TGF-β		 ↓Angiogenesis
↑ECM remodeling

Prostacyclin (PGI2) is released by healthy endothelial cells and performs its function through a paracrine signaling cascade that involves G protein-coupled receptors on nearby platelets and endothelial cells. The platelet Gs protein-coupled receptor (prostacyclin receptor) is activated when it binds to PGI2. This activation, in turn, signals adenylyl cyclase to produce cAMP. cAMP goes on to inhibit any undue platelet activation (in order to promote circulation) and also counteracts any increase in cytosolic calcium levels that would result from thromboxane A2 (TXA2) binding (leading to platelet activation and subsequent coagulation). PGI2 also binds to endothelial prostacyclin receptors and in the same manner raise cAMP levels in the cytosol. This cAMP then goes on to activate protein kinase A (PKA). PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase, which leads to smooth muscle relaxation and vasodilation. It can be noted that PGI2 and TXA2 work as physiological antagonists.

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