TABLE 1.
Targets and sites of action of ATP and SNO within and exported by RBCs.
| ATP roles within the RBC | Proximal Source | Target Cell | Physiologic/pathologic Process | Method of assay | References |
| Support metabolic needs | EMP, PPP | RBC | ATP-requiring enzymes such as those for antioxidant defense | HPLC/MS, luciferin/luciferase | Puchulu-Campanella et al., 2013 |
| Provide substrate for regulatory phosphorylation reactions | EMP, PPP | (RBC) | Regulation of solute transport, deformability | Phosphoproteomics, phosphoprotein-specific antibodies | Betz et al., 2009 |
| P2Y receptors: autocrine (negative feedback) G proteins | EMP, PPP | RBC surface | Feedback control of ATP export | ATP flux and receptor pharmacology and genetics | Wang et al., 2005 |
| Roles of ATP exported by the RBC | |||||
| P2X receptors | EMP, PPP | Leukocytes, endothelial cells | PMN activation; PMN adhesion | Receptor/ligand pharmacology | Dawicki et al., 1995 |
| Unknown | EMP, PPP | Endothelial cells | Inhibition of RBC-EC adhesion | n/a | Zhu et al., 2011 |
| Adenosine receptors after ectonucleotidase activity | ATP from EMP and PPP; ADO from ATPase action | Vascular smooth muscle cells; cardiomyocytes | Vasodilation; modulation of cardiac rhythm | Receptor/ligand pharmacology | Burnstock, 2015 |
| SNO roles within the RBC | |||||
| GAPDH: regulation of metabolism | Undetermined | RBC | Metabolic regulation | Biotin switch assay | Galli et al., 1998; Foster et al., 2003; Puchulu-Campanella et al., 2013 |
| Spectrin and other cytoskeletal proteins | Undetermined | RBC | Regulation of deformability; role in regulation of adhesion is undetermined | Biotin switch assay | Grau et al., 2013; Riccio et al., 2015 |
| Hemoglobin | Endothelial NO; eNOS in RBCs; NO2– | RBC | Allosteric coupling of RBC delivery of O2 and vasodilator SNO | MPC SNO assays; mouse genetics; SO2 gradient clamping | Jia et al., 1996; McMahon et al., 2002; Luchsinger et al., 2005; Cortese-Krott et al., 2012 |
| AE1 (anion exchanger) aka Band 3 | Hb-bound SNO | RBC | Membrane-resident stationing of low-mass SNO for export by RBC | Pharmacologic probes | Pawloski et al., 2001 |
| Pannexin 1 | Undetermined | RBC | (S)NO regulation of ATP export | Biotin switch assay | Lohman et al., 2012 |
| Roles of SNO exported by the RBC | |||||
| Soluble guanylate cyclase in vascular smooth muscle | RBC SNO | VSMC | RBC potentiation of hypoxic vasodilation | Pharmacologic inhibitors | McMahon et al., 2005 |
| Platelet activation signaling elements | RBC SNO | PLT | Inhibition of platelet aggregation | Platelet aggregometry | Pawloski et al., 1998 |
| Leukocyte adhesion receptors/ligands | RBC SNO | WBC | Modulation of sickle RBC-driven leukocyte adhesion by NO/SNO | Receptor/ligand antagonists | McMahon et al., 2019 |
| Endothelial adhesion receptors | RBC SNO | EC | Modulation of RBC-EC adhesion | Pharmacologic inhibitors | Dosier et al., 2017 |