LOW CONCENTRATIONS OF SODIUM-FLUORIDE INHIBIT CA-2-MEDIATED PLATELET ACTIVATION( INFLUX INDUCED BY RECEPTOR)

Sodium fluoride (NaF) alone below the concentration of 10 mM had no ef fect on platelet intracellular Ca2+([Ca2+]i). When platelets were incu bated with low concentrations of NaF (< 10 mM) prior to thrombin stimu lation, the second phase of [Ca2+]i elevation which is attributable to Ca2+ influx was suppressed, while the initial rapid peak of [Ca2+]i w hich is attributable to internal Ca2+ release was unaffected. Ca2+ inf lux assessed by the addition of extracellular Ca2+ to cells preactivat ed by thrombin in the absence of extracellular Ca2+ was also inhibited by NaF in a dose-dependent manner. NaF was also effective in inhibiti ng 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 thapsigargi n, a Ca2+-ATPase inhibitor, was only partially suppressed by NaF treat ment. It is suggested that Ca2+ entry induced by receptor-mediated act ivation is NaF-senstive and that the depletion of Ca2+ storage sites b y artificial procedures facilitates the opening of Ca2+ channels via N aF-insensitive pathways.