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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. Review. | Ting and Khasawneh Journal of Biomedical Science 2010 17 24 http www.jbiomedsci.eom content 17 1 24 I NSC The cost of publication in Journal of Biomedical Science is bourne by the National Science Council Taiwan. JOURNAL OF BIOMEDICAL SCIENCE REVIEW Open Access Platelet function and Isoprostane biology. Should Isoprostanes be the newest member of the Orphan-ligand family Harold J Ting and Fadi T Khasawneh 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. Review Maintaining proper function of platelets is vital as their primary task is to stop bleeding from an injured vessel a process known as hemostasis 1 2 . The hemostatic plug that forms in order to halt blood loss must be capable of rapid dissolution upon wound healing 3 . Nonetheless blood flow must remain unimpeded in all other instances to ensure effective nutrient and waste exchange. Thus platelets are necessarily firmly regulated blood elements that must be highly and quickly responsive to activating stimuli but otherwise are completely quiescent. Malfunctions in either of these behaviors leads to a host of disorders 3 4 . Furthermore various deficiencies in activation result in bleeding diseases which are associated with morbidity and mortality and may require lifetime treatment e.g. von Willebrand disease 4 5 . Conversely improper activation or recruitment of platelets to sites where hemostasis is not needed are hallmarks of myocardial infarction ischemic stroke .