The effects of pentoxifylline on rat erythrocytes of different age.
Age-separated rat erythrocytes were exposed to pentoxifylline, a dimethylxanthine derivative which increases erythrocyte deformability. A comparison of drug-induced effects in young and old erythrocytes yielded age-specific alterations in: (1) accumulation of intracellular Ca2+; (2) membrane protein phosphorylation; (3) ATP concentrations; and (4) membrane associated protein kinase activity. The effect of Ca2+ accumulation and membrane protein phosphorylation appears to be biphasic. Low drug concentrations (0.5-2.5 mM) reduced intracellular Ca2+ and increased membrane protein phosphorylation, whereas higher concentrations (4.0-5.0 mM) increased Ca2+ levels and reduced membrane protein phosphorylation. Young cells exhibited increased ATP levels over the whole range of pentoxifylline tested; however, older erythrocytes demonstrated higher ATP levels at 5.0 mM drug only. Membrane-associated protein kinase activity was enhanced 10% in young erythrocytes at 1.0 mM pentoxifylline and decreased to 30% of control values at 4.0 and 5.0 mM drug. Protein kinase of old erythrocytes exhibited gradual inhibition over the entire drug concentration range. In general, younger erythrocytes appear to be more responsive to pentoxifylline exposure. Based on these studies, it appears that the ageing of the erythrocyte and loss of deformability in vivo may be a consequence of increased Ca2+ entry into the cell.
D000818:Animals; D002118:Calcium / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D004905:Erythrocyte Aging; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000097:blood / Q000302:isolation & purification; D008970:Molecular Weight; D010431:Pentoxifylline / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000097:blood; D010766:Phosphorylation; D011494:Protein Kinases / Q000097:blood; D051381:Rats; D013805:Theobromine / Q000031:analogs & derivatives*
D008565:Membrane Proteins; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D013805:Theobromine; D010431:Pentoxifylline; D002118:Calcium