Characteristics and regulation of ganglioside-induced elevation of free cytoplasmic Ca2+ in human blood platelets.
We have found that gangliosides GD3 and GM3 induced rapid, reversible elevation of free cytoplasmic Ca2+ in fura-2-loaded human blood platelets. The effect persisted in Ca(2+)-free medium, indicating that gangliosides stimulated mobilization of intracellular stores. The action of gangliosides was concentration-dependent with EC50 of about 1 microM. The Ca(2+)-mobilizing effects of gangliosides were potentiated by epinephrine and inhibited by substances inducing activation of protein kinase C and cAMP-dependent protein kinases. Acidic phospholipids partially mimicked the Ca(2+)-mobilizing effects of gangliosides indicating that lipid head charge is essential for this activity. While the elevation of [Ca2+]i produced by arachidonic acid was almost completely blocked by aspirin pretreatment, the effects of gangliosides were diminished only 2-fold, indicating that gangliosides activate both aspirin-sensitive and aspirin-insensitive mechanisms of [Ca2+]i elevation.
Vasylevskaya
V V
VV
Institute of Experimental Cardiology, Academy of Medical Sciences, Moscow, Russia.
Bochkov
V N
VN
Prokazova
N V
NV
Tkachuk
V A
VA
D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D016257:Fura-2; D005679:G(M3) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D006801:Humans; D010743:Phospholipids / Q000494:pharmacology; D015854:Up-Regulation
D005679:G(M3) Ganglioside; D005732:Gangliosides; D010743:Phospholipids; D016718:Arachidonic Acid; C026226:ganglioside, GD3; D001241:Aspirin; D002118:Calcium; D016257:Fura-2; D004837:Epinephrine