Nitric Oxide Uptake by Erythrocytes Is Primarily Limited by Extracellular Diffusion Not Membrane Resistance*

The process of NO transfer into erythrocytes (RBCs) is of critical biological importance because it regulates the bioavailability and diffusional distance of endothelial-derived NO. It has been reported that the rate of NO reaction with oxyhemoglobin (Hb) within RBCs is nearly three orders of magnitude slower than that by equal amounts of free oxyhemoglobin. Consistent with early studies on oxygen uptake by RBCs, the process of extracellular diffusion was reported to explain this much lower NO uptake by RBC encapsulated Hb (Liu, X., Miller, M. J., Joshi, M. S., Sadowska-Krowicka, H., Clark, D. A., and Lancaster, J. R., Jr. (1998) J. Biol. Chem. 273, 18709–18713). However, it was subsequently proposed that the RBC membrane provides the main resistance to NO uptake rather than the process of extracellular diffusion (Vaughn, M. W., Huang, K. T., Kuo, L., and Liao, J. C. (2000) J. Biol. Chem. 275, 2342–2348). This conclusion was based on competition experiments that were assumed to be able to determine the rate constant of NO uptake by RBCs without extracelluar diffusion limitation. To test the validity of this hypothesis, we theoretically analyzed competition experiments. Here, we show that competition experiments do not eliminate the extracellular diffusion limitation. Simulation of the competition data indicates that the main resistance to NO uptake by RBCs is caused by extracellular diffusion in the unstirred layer surrounding each RBC but not by the RBC membrane. This extracellular diffusion resistance is responsible for preventing interference of NO signaling in the endothelium without the need for special NO uptake by intracellular hemoglobin or a unique membrane resistance mechanism.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-07-19

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M201939200PMID 12006567
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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