Low concentrations of sodium fluoride inhibit Ca 2+ influx induced by receptor-mediated platelet activation

Abstract

Sodium flouride (NaF) alone below the concentration of 10 mM had no effect on platelet intracellular Ca 2+ ([Ca 2+] i. When platelets were incubated with low concentrations of NaF (< 10 mM) prior to thrombin stimulation, the second phase of [Ca 2+] i elevation which is attributable to Ca 2+ influx was suppressed, while the initial rapid peak of [Ca 2+] 1 which is attributable to internal Ca 2+ release was unaffected. Ca 2+ influx assessed by the addition of extracellular Ca 2+ to cells preactivated by thrombin in the absence of extracellular of Ca 2+ was also inhibited by NaF in a dose-dependent manner. NaF was also effective in inhibiting thrombin- or U-46619-induced Mn 2+ entry. This inhibitory effect of NaF on Ca 2+ influx occurred after a lag of at least 30 s. However, Ca 2+ influx induced by ionomycin-induced Ca 2+ depletion or by thapsigargin, a Ca 2+-ATPase inhibitor, was only partially suppressed by NaF treatment. It is suggested that Ca 2+ entry induced by receptor-mediated activation is NaF-senstive and that the depletion of Ca 2+ storage sites by artificial procedures facilitates the opening of Ca 2+ channels via NaF-insensitive pathways.