Low concentrations of sodium fluoride inhibit Ca2+ influx induced by receptor-mediated platelet activation

Sodium fluoride (NaF) alone below the concentration of 10 mM had no effect on platelet intracellular Ca2+ ([Ca2+]i). When platelets were incubated with low concentrations of NaF (< 10 mM) prior to thrombin stimulation, the second phase of [Ca2+]i elevation which is attributable to Ca2+ influx was suppressed, while the initial rapid peak of [Ca2+]i which is attributable to internal Ca2+ release was unaffected. Ca2+ influx assessed by the addition of extracellular Ca2+ to cells preactivated by thrombin in the absence of extracellular Ca2+ was also inhibited by NaF in a dose-dependent manner. NaF was also effective in inhibiting thrombin- or U-46619-induced Mn2+ entry. This inhibitory effect of NaF on Ca2+ influx occurred after a lag of at least 30 s. However, Ca2+ influx induced by ionomycin-induced Ca2+ depletion or by thapsigargin, a Ca(2+)-ATPase inhibitor, was only partially suppressed by NaF treatment. It is suggested that Ca2+ entry induced by receptor-mediated activation is NaF-sensitive and that the depletion of Ca2+ storage sites by artificial procedures facilitates the opening of Ca2+ channels via NaF-insensitive pathways.