Platelet function and Isoprostane biology. Should Isoprostanes be the newest member of the Orphan-ligand family?

Abstract

While there have been many reports investigating the biological activity and signaling mechanisms of isoprostanes, their role in biology, particularly in platelets, appears to still be underestimated. Moreover, whether these lipids have their own receptors is still debated, despite multiple reports that discrete receptors for isporpstanes do exist on platelets, vascular tissues, amongst others. This paper provides a review of the important literature of isoprostanes and provides reasoning that isoprostanes should be classified as orphan ligands until their receptor(s) is/are identified.

Glucagon-like peptide-1 preserves coronary microvascular endothelial function after cardiac arrest and resuscitation: potential antioxidant effects

“…In addition to its role as a marker of oxidant stress, 8-iso-PGF 2␣ is also a potent vasoconstrictor in a variety of vascular beds (24, 26, 38,49,52,94,102). Therefore, enhanced postresuscitation microvascular function in the heart by GLP-1 could be related to improved responses to endogenous vasodilating signals, as well as to decreased production of endogenous vasoconstricting agents, or both.…”

Platelet thromboxane (11-dehydro-Thromboxane B2) and aspirin response in patients with diabetes and coronary artery disease

“…If ingesting ASA, platelet hyperactivity would be induced by COX-2 and 8-isoPGF2α alone. Limited or no COX-1 TxA2 production after ASA ingestion would leave unoccupied TPR available to bind 8-isoPGF2α that has a longer half-life (1-10 min vs 20-30 s) and higher plasma concentration (351-1831 vs 1-66 pg/mL) than TxA2 [6] . Thus, blocking F2-isoprostane derived from oxidative inflammatory pathways not affected by ASA may be considered in CVD management especially in those individuals with poor ASA response.…”

“…The latter function is accomplished by TxA2 binding to thromboxane platelet receptors (TPR), a typical G protein-coupled receptor system with trans-membrane segments. Once bound to TPR receptors, phospholipase C is activated to stimulate cytoplasmic Ca 2+ -dependent Rho Kinases that activate phospholipase A2 and the up-regulation and expression of glycoprotein complex GPⅡb/Ⅲa on the surface of platelets [5,6] . Because TxA2 is the bioactive and clinically relevant pro-thrombotic thromboxane metabolite, it would be the logical choice for testing in the clinical laboratory.…”

Is There Still a Role for Glycoprotein IIb/IIIa Antagonists in Acute Coronary Syndromes?

“…Because of the low affinity for ligands in resting platelets and its increase after platelets are activated, being GP IIb/IIIa the final common pathway of platelet aggregation [4] it soon became the target for specific and rationally elaborated antiplatelet drugs [1]. …”