Adenosine signals through ADORA2B to induce erythrocyte SphK1 activity increase. (A) SphK1 activity in cultured primary erythrocytes from 4 adenosine receptor-deficient mice after NECA (10 μM) treatment for 30 min. (B-E) SphK1 activity in cultures of primary erythrocytes from (B) WT mice, (C) normal human subjects, (D) SCD transgenic mice, and (E) SCD patients after NECA (10 μM) treatment with and without AODRA2B antagonist MRS1754 (10 μM). Values shown represent the mean ± SEM (n = 5 for SCD patients and normal human subjects; n = 6 for SCD transgenic mice and WT mice). *P < .05 NECA vs NECA + MRS 1754 or NECA vs control.