The effects of pentoxifylline on the plasma membrane Ca2+ ATPase in age-separated rat and human erythrocytes.

Abstract

Pentoxifylline, a dimethyl xanthine derivative given to patients with peripheral vascular disorders, increases erythrocyte deformability, diminishes Ca2+ entry, inhibits Ca(2+)-dependent transglutaminase activity and elevates ATP levels. The present study examined the effects of pentoxifylline on the Ca2+ pump ATPase, an enzyme which regulates intracellular Ca2+ levels. Studies were carried out with inside-out vesicles (IOVs) prepared from young (Ey) and old (Eo) human and rat erythrocytes. The pumping of Ca2+ depends on the concomitant hydrolysis of ATP; the two processes were measured using radiolabeled substrates. The catalytic properties of IOVs from young and old erythrocytes were stimulated by pentoxifylline when added directly to the assay medium. Pentoxifylline (0.5 to 5.0 mM) significantly activated the rates of Ca2+ dependent ATP hydrolysis in Ey and Eo IOVs of rat erythrocytes. The percent of activation was greater in the IOVs from older erythrocytes. The Ca2+ translocation was also affected by pentoxifylline. The early burst of Ca2+ uptake into IOVs decreased in the presence of pentoxifylline in Ey IOVs prepared from either species whereas steady state rates of Ca2+ transport only declined at 5.0 mM pentoxifylline. This pattern was not evident in the corresponding Eo IOVs. The response of Ey and Eo IOVs to pentoxifylline may be the basis of the difference in sensitivity of young and old erythrocytes to the drug in regulating intracellular Ca2+ concentrations.