BACKGROUND: During neurogenic inflammation, neuro-peptides (substance P, SP, calcitonin gene-related peptide, CGRP, and neurokinin A) are released from nerve endings, and these peptides initiate inflammatory reactions in the microcirculation. Platelets are one of the most important elements of the microcirculation. METHODS: Our in vitro experiments were carried out to determine the effects of inflammatory neuropeptides (SP, and CGRP) on the arachidonate cascade of isolated rat platelets. Cells were labeled with 1-14C-arachidonic acid, then the eicosanoids were separated with overpressure thin-layer chromatography or high-performance liquid chromatography and were quantitatively determined with a liquid scintillation analyzer. RESULTS: SP (10(-9) and 10(-8) mol/l) significantly increased the activity of the arachidonate cascade. The lipoxygenase pathway was significantly stimulated by SP (10(-11), 10(-9) and 10(-8) mol/l), while the cyclooxygenase system was inhibited by 10(-12) mol/l, and stimulated by 10(-9) mol/l SP. The dose-response curve of TxA2 to SP exhibited a similar pattern to that detected for the cyclooxygenase pathway. Among the vasodilator cyclooxygenase metabolites, only the synthesis of PGE2 was significantly elevated by SP (10(-9) mol/l ). CGRP either in low (10(-12)-10(-11) mol/l) or in high concentrations (10(-6) mol/l) activated the cyclooxygenase pathway, while it had no effect on the lipoxygenase pathway. CGRP (8-37), a specific CGRP1 receptor antagonist, inhibited the effects of CGRP. CONCLUSIONS: Our data suggest that the arachidonate metabolites of platelets may play a role in the process of neurogenic inflammation.

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Effect of 19-norsteroids on the motility of human fallopian tubes.

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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.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗