Adrenaline potentiates PI 3-kinase in platelets stimulated with thrombin and SFRLLN: role of secreted ADP

• Published in: FEBS letters Vol. 485; no. 1; pp. 62 - 66
• Main Authors: Selheim, Frode, Frøyset, Ann Kristin, Strand, Ingrid, Vassbotn, Flemming S, Holmsen, Holm
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 17.11.2000
• Subjects: ACD, acid citrate dextrose; Adenosine Diphosphate - metabolism; Adenosine Triphosphate - metabolism; Adrenaline; Blood Platelets - drug effects; Blood Platelets - enzymology; CP, creatine phosphate; CPK, creatine phosphokinase; Drug Synergism; Epinephrine - pharmacology; GFP, gel-filtered platelets; GroPIns, glycerophosphoinositols; HPLC, high performance liquid chromatography; Humans; Oligopeptides - pharmacology; Peptide Fragments - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Phosphatidylinositol Phosphates - biosynthesis; Phosphoinositide 3-kinase; PI3K, phosphoinositide 3-kinase; Platelet Activation - drug effects; Platelet Aggregation - drug effects; PRP, platelet-rich plasma; PtdIns(3,4)P2, phosphatidylinositol 3,4-bisphosphate; PtdIns(3,4,5)P3, phosphatidylinositol 3,4,5-trisphosphate; PtdIns(4,5)P2, phosphatidylinositol 4,5-bisphosphate; PtdIns, phosphatidylinositol; Thrombin - pharmacology; TLC, thin layer chromatography; PI3K, phosphoinositide 3-kinase; PRP, platelet-rich plasma; Adrenaline; GFP, gel-filtered platelets; TLC, thin layer chromatography; PtdIns(3,4,5)P 3, phosphatidylinositol 3,4,5-trisphosphate; CP, creatine phosphate; PtdIns(3,4)P 2, phosphatidylinositol 3,4-bisphosphate; HPLC, high performance liquid chromatography; PtdIns, phosphatidylinositol; Phosphoinositide 3-kinase; ACD, acid citrate dextrose; CPK, creatine phosphokinase; GroPIns, glycerophosphoinositols; PtdIns(4,5)P 2, phosphatidylinositol 4,5-bisphosphate
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)02188-8

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.