The effect of substance P on the arachidonate cascade of rat platelets.
The role of substance P (SP) in neurogenic inflammation is well known. Through neurokinin receptors, SP activates cells, including the arachidonate cascade of platelets. Our in vitro experiments were carried out to determine the effect of SP on the arachidonate cascade of rat platelets. The platelets were labelled with 14C-arachidonic acid, and the 14C-eicosanoids were then separated by means of overpressure thin-layer chromatography or high-performance liquid chromatography and were quantitatively determined. SP (10(-9) and 10(-8)) mol/L significantly increased the rate of the arachidonate cascade. The lipoxygenase pathway of platelets was stimulated by SP, which can result in the activation of protein kinase C mediated intracellular events. The cyclooxygenase system was inhibited by 10(-12) mol/L, and stimulated by 10(-9) mol/L SP. In our experiments SP in the physiological range of plasma concentration (10(-12) mol/L) decreased the synthesis of vasoconstrictor arachidonate metabolites (TxA2 and PGF2 alpha). These data suggest that in physiologic conditions the arachidonate cascade of platelets may play role in the vasodilator effect of SP. The formation of thromboxane in rat platelets was stimulated by higher concentration of SP (10(-9) mol/L), and therefore the SP-induced cytotoxicity against parasites might be mediated by the stimulation of thromboxane A2 synthesis.
Department of Pathophysiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
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Telegdy
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000097:blood; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000097:blood; D008084:Lipoxygenase / Q000097:blood; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000097:blood
D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D015289:Leukotrienes; D016718:Arachidonic Acid; D013373:Substance P; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013928:Thromboxane A2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C021201:12-HPETE; D015237:Dinoprost; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone