Platelet aggregating response to platelet activating factor participates in activation of the 12-lipoxygenase pathway in platelets from rabbits.
BACKGROUND
Many thrombotic angiopathies are known to originate from abnormalities in platelet-blood vessel interaction. The present study focuses on the platelet activating factor (PAF)-induced platelet aggregating mechanism and the arachidonate metabolic pathways activated by it in platelets from a male rabbit.


METHODS
Blood vessel contractility was examined using perfused arterial segments dissected from rabbit ear central arteries. Autologous platelet rich plasma (PRP) was infused into the perfusion system. Vascular contractilities were examined during infusion of PRP with a platelet agonist such as collagen or PAF. Platelet aggregation was measured with a platelet aggregometer.


RESULTS
Vasocontractile response to noradrenaline (NA) during infusion of PRP with PAF was initially augmented but gradually became attenuated, whereas repetitive vasocontractile responses to NA in the presence of PRP with collagen gradually increased. Platelet aggregation in response to PAF was moderately inhibited by both nordihydroguaiaretic acid (NDGA) and baicalein, 12-lipoxygenase (LOX) inhibitors, was unaffected by indomethacin (IM), a cyclo-oxygenase (COX) inhibitor, and was markedly diminished by EGTA, a calcium chelator.


CONCLUSIONS
PAF-induced platelet aggregation may participate in the activation of the 12-LOX pathway rather than the COX pathway in platelets, and is remarkably sensitive to intracellular Ca2+ levels.
Michibayashi
T
T
Clinical Pathophysiology, Division of Human Comprehensive Medicine, Graduate School of Medicine, Sapporo Medical University, Japan.
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000187:drug effects* / Q000502:physiology*; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D010972:Platelet Activating Factor; D014662:Vasoconstrictor Agents; D003094:Collagen; D001092:Arachidonate 12-Lipoxygenase; D009638:Norepinephrine