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.
Department of Clinical and Laboratory Medicine, Yamanashi Medical College, Japan.
Y
Y
Ozaki
K
K
Satoh
Y
Y
Yatomi
S
S
Kume
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects; D006801:Humans; D008345:Manganese / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D015539:Platelet Activation; D011956:Receptors, Cell Surface / Q000502:physiology*; D012969:Sodium Fluoride / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers; D013917:Thrombin / Q000494:pharmacology
D015220:Calcium Channels; D002352:Carrier Proteins; D011956:Receptors, Cell Surface; D017923:Sodium-Hydrogen Exchangers; D008345:Manganese; D012969:Sodium Fluoride; D013917:Thrombin; D002118:Calcium