Binding of oxpentifylline to the erythrocyte membrane and effects on cell ATP, cation content, and membrane area

Issue title: Memorial Issue for Robin Fåhraeus (1888–1968)

Article type: Research Article

Authors: Bilto, Y.Y.^{a; b; c} | Ellory, J.C.^{a; b; c} | Player, M.^{a; b; c} | Stuart, J.^{a; b; c; *}

Affiliations: [a] Department of Haematology, Medical School, University of Birmingham, Birmingham B15 2TJ, UK | [b] Department of Physiology, University of Oxford, Oxford OXl 3PT, UK | [c] Department of Biological Sciences, University of Jordan, Amman, Jordan

Correspondence: [*] Correspondence to Professor J. Stuart, Birmingham.

Note: [] Accepted by: Editor J.A. Dormandy

Abstract: Erythrocyte ATP was partially depleted by incubating normal human erythrocytes at 37°C for 24 hours. Incubation in the presence of 5 mmol/l oxpentifylline caused further depletion of ATP irrespective of whether membrane Na+/K+ pump or Na+/K+/Cl− cotransport activities were inhibited and whether glycolysis was stimulated or inhibited. Similar depletion of erythrocyte ATP was found by incubating erythrocytes with either metabolite I of oxpentifylline, the rheologically active oxpentifylline analogue A81 3138, or the rheologically inactive natural methylxanthine theophylline. Partitioning of 14C-oxpentifylline into the erythrocyte membrane was demonstrated but this did not increase membrane surface area as tested by hypotonic stress. Thus the rheological action of oxpentifylline at 37°C, which is associated with inhibition of K+ efflux from erythrocytes, is a membrane-associated event and does not involve an increase in cell ATP content.

Keywords: Rheology, Erythrocyte deformability, Oxpentifylline, Ion channels

DOI: 10.3233/CH-1988-8611

Journal: Clinical Hemorheology and Microcirculation, vol. 8, no. 6, pp. 901-912, 1988