Effect of intracellular Na+ on platelet aggregation and Ca2+ mobilization.
The effects of ionophores, which can carry alkali metal cations, on platelet aggregation were examined. At an alkaline extracellular pH, alkali metal cation/H+ exchanger nigericin accelerated aggregation in K+-enriched medium, whereas it rather inhibited aggregation in Na+-enriched medium, even though the intracellular pH was only slightly alkaline. The inhibitory effect of Na+ on platelet aggregation was more clearly shown with the alkali metal cation exchanger gramicidin D. The ionophore had no effect or a slightly accelerative effect on aggregation in K+-enriched medium, whereas it significantly inhibited aggregation induced by thrombin, ADP and platelet activating factor in Na+-enriched medium. Fluorescence studies on fura-2-labeled platelets revealed that in Na+-enriched medium gramicidin D inhibited agonist-induced Ca2+ mobilization both in the presence and absence of extracellular Ca2+. These results suggest that the intracellular Na+ inhibits platelet aggregation by inhibiting Ca2+ mobilization.
Kitagawa
S
S
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Usui
K
K
Kametani
F
F
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood; D002417:Cattle; D003600:Cytosol / Q000378:metabolism; D006096:Gramicidin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009550:Nigericin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011188:Potassium / Q000502:physiology; D012964:Sodium / Q000502:physiology*; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D006096:Gramicidin; D012964:Sodium; D009550:Nigericin; D011188:Potassium; D002118:Calcium