OXPENTIFYLLINE-INDUCED INHIBITION OF CALCIUM-ENTRY INTO HUMAN ERYTHROCYTES

The rheological action in human erythrocytes of oxpentifylline, a synt hetic dimethyl xanthine, has been studied using blood from healthy con trols and from patients with sickle cell anaemia. Calcium flux measure ments using 45Ca and the dihydropyridine D-600 (methoxyverapamil) were used to define a specific fraction of Ca entry into human erythrocyte s. Oxpentifylline was found to inhibit the D-600-sensitive Ca flux (IC 50 in the order of 0.5 mM) and may therefore protect sickle cells agai nst Ca-mediated dehydration. Sickle cells were then dehydrated by 15 h ours of cyclical oxygenation-deoxygenation in Ca-containing buffer. Ox pentifylline (1 muM-5 mM) failed to prevent Ca-induced loss of cation via the K efflux (Gardos) channel. Thus the inhibitory effect of oxpen tifylline on mediated Ca-entry is insufficient to prevent Ca-dependent dehydration of sickle cells. Inhibition of the Gardos channel in addi tion would seem to be necessary for a significant anti-sickling effect .