Inositol 1,4,5-trisphosphate (IP3) induced rapid formation of thromboxane B2 in saponin-permeabilised human platelets: mechanism of IP3 action.
The mechanism of IP3-induced activation of saponin-permeabilised platelets has been examined. Saponin permeabilization resulted in the leakage of low-Mr substances into and from the cells without loss of cytoplasmic proteins. Addition of IP3 rapidly induced a dose-related formation of thromboxane B2 and release into the medium, leading to the responses of shape change, aggregation and [14C]5HT release. These responses were inhibited by the thromboxane A2 receptor antagonist AH23848. The IP3-induced release of 45Ca from intracellular stores was not affected by indomethacin. Synthesis of thromboxane was inhibited if Ca2+ elevation was prevented by using Ca-EGTA buffers during permeabilization. These studies indicate that IP3-induced activation was due to Ca2+ mobilisation leading to phospholipase activation and thromboxane synthesis.
D001713:Biphenyl Compounds / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D008970:Molecular Weight; D011982:Receptors, Prostaglandin / Q000378:metabolism; D017482:Receptors, Thromboxane; D012503:Saponins; D012701:Serotonin / Q000378:metabolism; D013403:Sugar Phosphates / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood*
D001713:Biphenyl Compounds; D007295:Inositol Phosphates; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D012503:Saponins; D013403:Sugar Phosphates; D012701:Serotonin; D000001:Calcimycin; D013929:Thromboxane B2; C046926:AH 23848; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium