Arg60 Leu Mutation in the First Cytoplasmic Loop of the Platelet Thromboxane A2 Receptor Is Not Essential for Mediating Inhibitory Coupling between the Receptor and Adenylyl Cyclase

Human platelet thromboxane A2 (TXA2) receptor (TXR) has been reported to functionally couple to the inhibitory GTP-binding protein for adenylyl cyclase (Gi). However, it still remains unclear which portions of the TXR structure are critical determinants in that coupling. We have previously reported several patients with platelet dysfunction, whose platelets showed impaired coupling between TXR and phospholipase C caused by an Arg60 to Leu mutation in the first cytoplasmic loop. To investigate whether this portion is essential for mediating inhibitory coupling between TXR and adenylyl cyclase, we analyzed the inhibition by the TXA2 analog of the PGE1 or forskolin-induced platelet cAMP increase in patientsʹ platelets, and found that the inhibition occurred normally. This suggests that Arg60 in the first cytoplasmic loop of the TXR is not involved in TXR-Gi coupling.