title: Involvement of Rac in thromboxane A2‑induced human platelet activation: regulation of sCD40 ligand release and PDGF‑AB secretion.
abstract: We have previously shown that glycoprotein Ib/IX/V activation stimulates the release of the soluble CD40 ligand (sCD40L) via the generation of thromboxane A2 from human platelets. In the present study, the role of Rac, which is a member of the Rho family, was investigated in the thromboxane A2‑stimulated release of platelet‑derived growth factor (PDGF)‑AB and sCD40L in human platelets. U46619, a thromboxane receptor agonist, stimulated the activation of Rac time‑dependently in human platelets, and NSC23766, a selective inhibitor of the Rac‑guanine nucleotide exchange factor interaction, reduced the U46619‑induced platelet aggregation. NSC23766 markedly suppressed the U46619‑induced p38 mitogen-activated protein (MAP) kinase phosphorylation. The thromboxane A2‑induced release of PDGF‑AB and sCD40L was significantly suppressed by NSC23766 in a dose‑dependent manner. In addition, NSC23766 reduced the sCD40L release stimulated by ristocetin, a glycoprotein Ib/IX/V activator. These results indicate that Rac regulates the thromboxane A2‑induced stimulation of PDGF‑AB secretion and sCD40L release via the p38 MAP kinase in human platelets.
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Kageyama
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Doi
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Iida
authors.affiliation: Department of Intensive Care Medicine, Matsunami General Hospital, Gifu 501‑6062, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akamatsu
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Kuroyanagi
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Mizutani
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Department of Anesthesiology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iida
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D012310:Ristocetin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; D020662:Guanine Nucleotide Exchange Factors; C487513:NSC 23766; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; C095477:platelet-derived growth factor AB; D012310:Ristocetin; D023201:CD40 Ligand; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D048051:p38 Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins