Implications of the Molecular Basis of Prostacyclin Biosynthesis and Signaling in Pharmaceutical Designs
Prostacyclin (PGI(2)) is one of the major vascular protectors against thrombosis and vasoconstriction, caused by thromboxane A(2). Understanding the molecular mechanisms of PGI(2) biosynthesis and signaling is crucial to the development of therapeutic approaches to regulate PGI(2) functions. This review provides information regarding the most current advances in the findings of the molecular mechanisms for PGI(2) biosynthesis in the endoplasmic reticulum (ER) membrane through the coordination between PGI(2) synthase and its upstream enzymes, cyclooxygenase-1 (COX-1) or -2 (COX-2), and for PGI(2) signaling through its cell membrane receptors and nuclear peroxisome proliferator-activated receptors. The substrate presentation from the COXs to PGI(2) synthase and its cell membrane receptor/G protein coupling sites, as characterized by our group, are discussed in detail. The association between the regulation of the biosynthesis and signaling of PGI(2) with the pathophysiological processes of PGI(2)-related diseases is also discussed. The molecular knowledge of PGI(2) biosynthesis and signaling will help to design the next generation of drugs, specifically targeting the regulation of PGI(2) functions, which will undoubtedly provide advances in cardiovascular protection and the treatment of PGI(2)-related diseases.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.