Use of radiolabeled 2-methylthio-ADP to study P2Y receptors on platelets and cell lines.

Abstract

The use of radioactive 2-methylthio-ADP (2MeS-ADP) to study ADP receptors on platelets was first developed by MacFarlane et al. (1) in 1983. However, this technique may not have initially been pursued by many groups because of the relative paucity of studies into platelet ADP receptors and the absence of a commercially available radiolabeled ligand. From 1992 to 1994, a few papers described the use of 2MeS-ADP to demonstrate the antagonistic activity of clopidogrel on the platelet ADP receptor (2–4) and the presence of ADP receptors on megakaryocytoblastic cells (5). Since these initial reports, several groups have published studies describing the binding characteristics of 2MeS-ADP on platelets (6,7). Two different teams provided evidence for a defect of ADP receptor numbers in platelets from patients with a low sensitivity to ADP (8,9). Consequently, a variety of antiplatelet compounds have been evaluated as antagonists on platelet ADP receptors (10–13). A recent study has demonstrated the ability of P2Y12 to bind 2MeS-ADP, supporting its identity as the previously named P2TAC or low-affinity platelet ADP receptor (14).