Inhibitory Effects of a Novel Antiplatelet Agent, E5510, on Collagen-Induced Platelet-Derived Growth Factor Release and Aggregation of Human Platelets In Vitro

• Published in: Japanese Journal of Pharmacology Vol. 61; no. 1; pp. 7 - 12
• Main Authors: Nomoto, Ken-ichi, Saeki, Takao, Kogushi, Motoji, Kobayashi, Hiroko, Fujimori, Tohru, Yamatsu, Isao
• Format: Journal Article
• Language: English; Japanese
• Published: Kyoto The Japanese Pharmacological Society 1993; Japanese Pharmacological Society
• Subjects: aggregation; Animals; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood. Blood coagulation. Reticuloendothelial system; Cell Division - drug effects; Cell proliferation; Cells, Cultured; collagen; Collagen - pharmacology; E5510; effects on; Fatty Acids, Monounsaturated - administration & dosage; Fatty Acids, Monounsaturated - pharmacology; Humans; induction; man; Medical sciences; Muscle, Smooth - cytology; Muscle, Smooth - drug effects; Pharmacology. Drug treatments; Platelet (human); Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet-derived growth factor; Platelet-Derived Growth Factor - metabolism; platelets; Radioimmunoassay; Rats; Rats, Sprague-Dawley; release; Smooth muscle cell; Smooth muscle cell; Cell proliferation; E5510; Platelet-derived growth factor; Platelet (human); Aggregation; Human; Platelet; Mechanism of action; In vitro; Platelet derived growth factor; Antiplatelet agent; Release
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.61.7

E5510, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid, is a new anti-platelet-aggregation agent under development. We examined the inhibitory efficacy of E5510 on PDGF-release from washed human platelets. E5510 concentration-dependently inhibited collagen-induced PDGF release from human platelets. PDGF release was reduced to below the detection limit (0.47 ng/ml) by preincubation of platelets with 0.04 μΜ or higher concentrations of E5510. Total growth factor release from platelets was also measured by a bioassay with cultured smooth muscle cells. E5510 almost completely abolished the mitogenic effect of collagen-induced platelet releasates at concentrations of 0.04 μΜ or higher. Our data suggest that the release of PDGF and other growth factors was inhibited by E5510 at the same concentration that inhibited platelet aggregation.