Specific Binding of Leptin to Red Blood Cells Delivers a Pancreatic Hormone and Stimulates ATP Release.

Since its discovery in 1994, leptin continues to have new potential physiological roles uncovered, including a role in the regulation of blood flow. Leptin's role in regulating blood flow is not completely understood. Red blood cell (RBC)-derived ATP is a recognized stimulus of blood flow, and multiple studies suggest that C-peptide, a hormone secreted in equimolar amounts with insulin from the pancreatic β-cells, can stimulate that release when delivered by albumin and in combination with Zn. Here, we report leptin delivers C-peptide and Zn to RBCs in a saturable and specific manner. We labeled leptin with technetium-99 m (Tc) to perform binding studies while using albumin to block the specific binding of Tc-leptin in the presence or absence of C-peptide. Our results suggest that leptin has a saturable and specific binding site on the RBC (( = 1.79 ± 0.46) × 10 M) that is statistically equal to the binding affinity in the presence of 20 nM C-peptide (( = 2.05 ± 0.20) × 10 M). While the binding affinity between leptin and the RBC did not change with C-peptide, the moles of bound leptin did increase with C-peptide, suggesting a separate binding site on the cell for a leptin/C-peptide complex. The RBC-derived ATP increased in the presence of a leptin/C-peptide/Zn addition, in a concentration-dependent manner. Control RBCs ATP release increased (71 ± 5.6%) in the presence of C-peptide and Zn, which increased further to (94 ± 5.6%) in the presence of Zn, C-peptide, and leptin.