Effects of inflammatory neuropeptides on the arachidonate cascade of platelets

Background: During neurogenic inflammation, neuropeptides (substance P,SP, calcitonin gene-related peptide, CGRP, and neurokinin A) are released from nerve endings, and these peptides initiate inflammatory reactions in the mi crocirculation. Platelets are one of the most important elements of the mic rocirculation. Methods: Our in vitro experiments were carried out to determ ine the effects of inflammatory neuropeptides (SP, and CGRP) on the arachid onate cascade of isolated rat platelets. Cells were labeled with 1-C-14-ara chidonic acid, then the eicosanoids were separated with overpressure thin-l ayer chromatography or high-performance liquid chromatography and were quan titatively determined with a liquid scintillation analyzer. Results: SP (10 (-9) and 10(-8) mol/l) significantly increased the activity of the arachido nate cascade. The lipoxygenase pathway was significantly stimulated by SP ( 10(-11), 10(-9) and 10(-8) mol/l), while the cyclooxygenase system was inhi bited by 10(-12) mol/l, and stimulated by 10(-9) mol/l SP. The dose-respons e curve of TxA(2) to SP exhibited a similar pattern to that detected for th e cyclooxygenase pathway. Among the vasodilator cyclooxygenase metabolites, only the synthesis of PGE(2) was significantly elevated by SP (10(-9) mol/ l). CGRP either in low (10(-12)-10(-11) mol/l) or in high concentrations (1 0(-6) mol/l) activated the cyclooxygenase pathway, while it had no effect o n the lipoxygenase pathway. CGRP (8-37), a specific CGRP1 receptor antagoni st, inhibited the effects of CGRP. Conclusions: Our data suggest that the a rachidonate metabolites of platelets may play a role in the process of neur ogenic inflammation.