Adrenaline potentiates PI 3-kinase in platelets stimulated with thrombin and SFRLLN: role of secreted ADP.
Adrenaline significantly potentiated late thrombin- and SFRLLN-induced PtdIns(3,4)P(2) production. Furthermore, the potentiating effect of adrenaline on thrombin-induced PtdIns(3, 4)P(2) production was independent on secreted ADP, whereas, the effect of adrenaline on SFRLLN-induced PtdIns(3,4)P(2) production was completely dependent of secreted ADP. However, the ADP-dependent accumulation of PtdIns(3,4)P(2) was not required for irreversible platelet aggregation induced by SFRLLN in the presence of adrenaline. It is concluded that adrenaline can replace secreted ADP to potentiate PtdIns(3,4)P(2) production in thrombin-stimulated but not in SFRLLN-stimulated platelets, thus demonstrating a qualitative difference between platelet stimulation by thrombin and the thrombin receptor activating peptide SFRLLN.
Selheim
F
F
Department of Biochemistry and Molecular Biology, University of Bergen, Norway.
Frøyset
A K
AK
Strand
I
I
Vassbotn
F S
FS
Holmsen
H
H
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology*
D009842:Oligopeptides; D010446:Peptide Fragments; D018129:Phosphatidylinositol Phosphates; C060980:phosphatidylinositol 3,4-diphosphate; C086309:thrombin receptor peptide SFLLRNP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C046617:arginyl-glycyl-aspartyl-serine; D019869:Phosphatidylinositol 3-Kinases; D013917:Thrombin; D004837:Epinephrine