Role of erythrocyte in regulating local O₂delivery mediated by hemoglobin oxygenation

Abstract

The release of ATP from red blood cells (RBC) in response to low O2 levels is linked to ATP production and the oxygenation state of hemoglobin. Because O2 is unloaded from the RBC, the concentration of deoxygenated hemoglobin increases, displacing phosphofructokinase from the cytoplasmic domain of band 3. We hypothesize that the ATP molecules produced through this glycolytic stimulation at the membrane surface result in the release of ATP from the RBC. Rat whole blood exposed to 5 min of low PO2 in vitro increased plasma [ATP] by 1.0 miccroM (+45%). This increase was reduced to 0.1 microM (+12%, P < 0.05) after citrate incubation and reversed after fluoride treatment (both glycolytic inhibitors) by -0.2 microM (-23%, P < 0.05). Plasma [ATP] of control RBC decreased -0.3 microM (-12%) when 8% CO (P < 0.05) was added to the chamber. Because CO and O2 bind competitively to heme, these results support our hypothesis that the release of ATP from RBC is linked to ATP production through the oxygenation state of the hemoglobin molecule.

Mechanisms for the control of local tissue blood flow during thermal interventions: influence of temperature‐dependent ATP release from human blood and endothelial cells

“…Conversely to our finding with heating, decreases in oxyhaemoglobin and $P_{{\mathrm{normalO}}_2}$ have repeatedly been shown to be strong stimuli for erythrocyte ATP release (Jagger et al . 2001; Sprague et al . 2009).…”

Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease

“…Since RBCs also export ATP [91], it becomes feasible to synthesize PAPS directly in the endothelial wall from ATP and sulfate. The PAPS, synthesized by endothelial cells, then becomes substrate for Ch-S synthesis by platelets adhering to the endothelial artery wall, as will be further discussed in section 4.3 on the atheroma.…”

The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and regulators of local blood flow

“…Mammalian RBCs release ATP when exposed to reduced oxygen tensions, and the amount released is linked to the decrease in Hb O 2 saturation (Ellsworth et al, 1995;Jagger et al, 2001). The extracellular ATP diffuses to the endothelium, where it binds to P 2y purinergic receptors, which activates the synthesis of vasodilators (including nitric oxide) that relax vascular smooth muscles and increase local blood flow and O 2 delivery (Ellsworth et al, 1995;Sprague et al, 2007).…”