Effects of inflammatory neuropeptides on the arachidonate cascade of platelets.
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.
Gecse
A
A
Department of Pathophysiology, Albert Szent-Györgyi Medical University, Szeged, Hungary. gecse@patph.szote.u-szeged.hu
Kis
B
B
Mezei
Z
Z
Telegdy
G
G
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000276:immunology; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000378:metabolism*
D013373:Substance P; D013928:Thromboxane A2; D015288:Neurokinin A; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015740:Calcitonin Gene-Related Peptide