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.

The role of plasma membrane CA sup 2 sup Pumps PMCAs in pathologies of mammalian cells

“…Pentoxyphilline also affected Ca 2+ uptake activity. The early burst of Ca 2+ uptake decreased in the vesicles from young but not from older erythrocytes (165).…”

Influence of Pentoxifylline on Sperm Membrane Functional Integrity

“…The nucleotide boosts the cellular glycolysis with rising endogenous ATP production. Nevertheless, other known effects cannot be discarded: e.g., modification of calcium transport [26], antagonism to endogenous adenosine actions [11], or inhibition of generation of reactive oxygen species [13,23,34] whose deleterious effects upon sperm functional activity have been previously reported [1].…”

Pentoxifylline Inhibits Pulmonary Fibrosis by Regulating Cellular Senescence in Mice

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