Proposed model for epinephrine-stimulated SS RBC adhesion to laminin.

During periods of stress, increased circulating levels of epinephrine act on the RBC β2-AR, thus activating Gα_s, which stimulates adenylyl cyclase (AC). This enzyme catalyzes the conversion of ATP to cAMP, leading to PKA activation, an intermediate step in the up-regulation of BCAM/Lu-mediated adhesion. (Phosphodiesterase [PDE] breaks down cAMP into AMP.) Events between PKA activation and enhancement of BCAM/Lu-mediated adhesion are currently unknown. Although this pathway may not be limited to RBCs from patients with sickle cell anemia, the vasculature of patients with sickle cell anemia probably exists in a much more pro-adhesive state. These factors acting in concert suggest that epinephrine-stimulated adhesion may play a clinically significant role in the context of sickle cell anemia.