N1-(Quinolin-2-ylmethyl) butane-1, 4-diamine, a polyamine analog: inhibition of platelet aggregation mediated by an elevated VASP, and decreased MAPK phosphorylation.

The current study intended to examine the signal transduction pathway of N-(quinolin-2-ylmethyl) butane-1, 4-diamine (QMA) in antiplatelet aggregation. Rats were divided randomly into five groups: control group; QMA-treated groups (0.3, 1, and 3 mg/kg); and r-Hirudin-treated group (0.3 mg/kg). Sample groups intravenously injected the corresponding agents once a day for 5 days; control group took 0.9% NaCl in the same way. Ten minutes after the last injection, blood samples were obtained from the rat abdominal aorta. Aggregation ex vivo was tested after irritating platelets by 1.5 U/ml thrombin for 5 min with a platelet aggregometer. Malondialdehyde production, activity of superoxide dismutase and nitric oxide production were determined by the microplate reader. Measurement of [Ca]i was performed using a fluorescence spectrophotometer. Thromboxane A2, cyclic adenosine monophosphate and cyclic guanosine monophosphate levels, vasodilator-stimulated phosphoprotein, and mitogen-activated protein kinase phosphorylation were measured with ELISA kits. Phospholipase C γ2 and protein kinase C were observed by immunoblotting study. QMA inhibited thrombin-induced platelet aggregation ex vivo. QMA significantly elevated superoxide dismutase activity, levels of cyclic adenosine monophosphate, cyclic guanosine monophosphate, nitric oxide, and subsequently promoted vasodilator-stimulated phosphoprotein phosphorylation. Meanwhile, QMA suppressed phospholipase C γ2, protein kinase C and mitogen-activated protein kinase phosphorylation, as well as malondialdehyde, thromboxane A2 formation and [Ca]i mobilization. QMA has a strong antiplatelet potential via its multitarget mechanism.