Oxpentifylline-induced inhibition of calcium entry into human erythrocytes

Abstract

The rheological action in human erythrocytes of oxpentifylline, a synthetic dimethyl xanthine, has been studied using blood from healthy controls and from patients with sickle cell anaemia. Calcium flux measurements using ⁴⁵Ca and the dihydropyridine D-600 (methoxyverapamil) were used to define a specific fraction of Ca entry into human erythrocytes. Oxpentifylline was found to inhibit the D-600-sensitive Ca flux (IC₅₀ in the order of 0.5 mM) and may therefore protect sickle cells against Ca-mediated dehydration. Sickle cells were then dehydrated by 15 hours of cyclical oxygenation-deoxygenation in Ca-containing buffer. Oxpentifylline (1 μM–5 mM) failed to prevent Ca-induced loss of cation via the K efflux (Gardos) channel. Thus the inhibitory effect of oxpentifylline on mediated Ca-entry is insufficient to prevent Ca-dependent dehydration of sickle cells. Inhibition of the Gardos channel in addition would seem to be necessary for a significant anti-sickling effect.