The potent endogenous inhibitor PGI₂ abolishes platelet Ca²⁺ responses to G protein-coupled receptors but not those after activation of GPVI, Toll-like receptors, or P2X1 cation channels. Effect of a supramaximal concentration of PGI₂ (60μM; 90 seconds) on [Ca²⁺]_i increases mediated via a range of receptors. Representative responses from more than 4 donors are shown in panels A through E, and the average as a percentage of a paired control is shown in panel F. The G protein–coupled receptor agonists U46619 (A,F; U4) and thrombin (B,F; Thr) were used at near-EC₅₀ concentrations (0.5μM U46619 and 0.03 U mL⁻¹ thrombin). GPVI and TLR2/1 receptor Ca²⁺ responses were stimulated with a low or intermediate concentration of collagen (0.5 and 2 μg mL⁻¹; C,F; Coll) or Pam₃CSK₄ (1 and 10 μg mL⁻¹, D,F; Pam), respectively. P2X1 receptors were maximally activated with 10μM α,βmeATP (E-F). The asterisks indicate significance levels compared with samples in the absence of PGI₂; the hash symbols indicate significance level compared with thrombin in the presence of PGI₂. U4 indicates U46619; Pam, Pam₃CSK₄; Thr, thrombin; and Coll, collagen.