Figure 7
Figure 7. The phosphodiesterase inhibitor cilostazol is an ABCC4 inhibitor that affects platelet aggregation. (A) PMEA accumulation and efflux assay was performed with Abcc4 WT and KO MEFs in the presence of varying concentrations of cilostazol. (B) PMEA export is inhibited by cilostazol comparable with MK571. The accumulation data are represented as the amount of [3H] PMEA (pmol) accumulated per mg of protein. The [3H] PMEA export data are presented as a percentage of total. (C) The impact of cilostazol on the aggregation of Abcc4 WT and KO platelets treated with collagen (P < .05). (D) Model depicting how cilostazol (pink half-circles) inhibits both PDE3 and ABCC4 to elevate cAMP (yellow circles). (E) Representative immunoblot of whole-cell lysates, prepared from Abcc4 WT and KO platelets treated with cilostazol, MK571, or cilostazol+MK571, forskolin (Fsk) 10 μM, and collagen 1 μg/mL for 30 minutes, probed with p-Vasp Ser 157 and total Vasp. (F) Quantification of p-Vasp Ser 157 phosphorylation as presented as ratio of p-Vasp Ser 157:total Vasp.

The phosphodiesterase inhibitor cilostazol is an ABCC4 inhibitor that affects platelet aggregation. (A) PMEA accumulation and efflux assay was performed with Abcc4 WT and KO MEFs in the presence of varying concentrations of cilostazol. (B) PMEA export is inhibited by cilostazol comparable with MK571. The accumulation data are represented as the amount of [3H] PMEA (pmol) accumulated per mg of protein. The [3H] PMEA export data are presented as a percentage of total. (C) The impact of cilostazol on the aggregation of Abcc4 WT and KO platelets treated with collagen (P < .05). (D) Model depicting how cilostazol (pink half-circles) inhibits both PDE3 and ABCC4 to elevate cAMP (yellow circles). (E) Representative immunoblot of whole-cell lysates, prepared from Abcc4 WT and KO platelets treated with cilostazol, MK571, or cilostazol+MK571, forskolin (Fsk) 10 μM, and collagen 1 μg/mL for 30 minutes, probed with p-Vasp Ser 157 and total Vasp. (F) Quantification of p-Vasp Ser 157 phosphorylation as presented as ratio of p-Vasp Ser 157:total Vasp.

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