Effects of Inflammatory Neuropeptides on the Arachidonate Cascade of Platelets

Abstract

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.

Substance P stimulates release of RANKL via COX-2 expression in human dental pulp cells

“…3). A recent study reported that the expression of SP may be related to PGE 2 in human gingival crevicular fl uid during periodontal infl ammation and the host response [42], and Gecse et al [43] found that SP also signifi cantly increases the activity of the arachidonate cascade. Those fi ndings are supported by our present results.…”

Tachykinins regulate the function of platelets

“…Our results are consistent with the observation that tachykinins, most particularly SP, can stimulate shape change in rabbit platelets. 17 Gecse et al 30,31 reported that SP could decrease the synthesis of thromboxane A 2 by platelets at picomolar concentrations. They also reported, however, an increased formation of thromboxane A 2 with higher concentrations of SP (nanomolar range).…”

Cerebrovascular Inflammation Following Subarachnoid Hemorrhage

“…This rise probably explains the fever usually found in SAH (60). The preferential production of PGE 2 may be explained by the fact that SP and CGRP stimulate the COX pathway in platelets and favor particularly the PGE2 pathway (92). A recent study showed that PGE 2 could be produced by microvessel endothelial cells in culture, probably through COX2 induction, after exposure to TNF-a (93).…”

“…Release of the sensory fiber transmitters SP and CGRP has been shown to occur after experimental SAH (6). In vitro, these peptides stimulate the AA cascade in platelets via both the lipoxygenase (SP only) and the COX (SP and CGRP) enzymes (92). Inversely, activated platelets have been shown to excite nociceptive C-fibers in a skin-nerve preparation (201).…”