Abstract
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 Ca 2+; (2) membrane protein prosphorylation; (3) ATP concentrations; and (4) membrane associated protein kinase activity. The effect of Ca 2+ accumulation and membrane protein phosphorylation appears to be biphasic. Low drug concentrations (0.5–2.5 mM) reduced intracellular Ca 2+ and increased membrane protein phosphorylation, whereas higher concentrations (4.0–5.0 mM) increased Ca 2+ 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 inbition 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 Ca 2+ entry into the cell.
Published Version
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