Role of autocrine stimulation for the effects of cyclic AMP on protein and lipid phosphorylation in platelets activated by particles

FEBS Letters

Ryningen, Anita¹  Holmsen, Holm¹ 

[1] Department of Biochemistry and Molecular Biology, University of Bergen, Årstadveien 19, N-5009 Bergen, Norway

关键词: Particulate agonist;    cAMP;    Autocrine inhibition;    Platelet response;    AHS;    acid hydrolase secretion;    cAMP;    cyclic 3′;    5′-adenosine monophosphate;    [cAMP]i;    intracellular level of cAMP;    CP;    creatine phosphate;    CPK;    creatine phosphate kinase;    DGS;    dense granular secretion;    ECL;    enhanced chemiluminescence;    GFP;    gel-filtered platelets;    HRP;    horseradish peroxidase;    IAS;    inhibitors of autocrine stimulation;    IEEC;    1′-(ethyloxycarbonyloxy)-ethyl-5-acetyl-amino-3-(N-methyl-acetylamino)-2;    4;    6 triiodo-benzenecarboxylate;    PA;    phosphatidic acid;    PGH2;    prostaglandin H2;    PI;    phosphatidylinositol;    PIP;    phosphatidylinositol 4-phosphate;    PIP2;    phosphatidylinositol 4;    5-bisphosphate;    PRP;    platelet-rich plasma;    TXA2;    thromboxane A2;   

DOI  :  10.1016/S0014-5793(98)01154-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have compared responses in platelets stimulated with the particulate materials, Intralipid (liposome-suspension) and a potential contrast medium IEEC (1′-(ethyloxycarbonyloxy)-ethyl-5-acetyl-amino-3-(N-methyl-acetylamino)-2,4,6-triiodo-benzenecarboxylate coated with human serum albumin), with and without forskolin and inhibitors of autocrine stimulation (IAS: an ADP-removing system of creatine phosphate/creatine phosphokinase; RGDS to prevent fibrinogen/fibronectin binding to GPIIb/IIIa; SQ 29.548 as a TXA₂ receptor antagonist; cyproheptadine as a serotonin receptor antagonist; BN 52021 as a platelet-activating factor receptor antagonist). The pattern of tyrosine-phosphorylated proteins, phosphorylation of initial lipids and phosphorylation of pleckstrin (P47) were used as markers for early signal transducing responses, while secretion of ADP+ATP and β-N-acetyl-glycosaminidase were used as final responses. Intralipid showed no platelet activation except for some weak tyrosine protein phosphorylation that was inhibited by elevated cAMP. IEEC induced strong platelet activation that was partly inhibited by increased levels of cAMP and IAS. The inhibition of elevated cAMP seemed to be due to removal of the G protein-mediated activation from secreted autocrine stimulators either by IAS or forskolin. The remaining activity is a pure effect from IEEC which is not affected by elevated cAMP.

【 授权许可】

Unknown