Role of platelet-activating factor in primary hemostasis.
To determine whether platelet-activating factor (PAF) has a physiological role in the process of primary hemostasis in the rabbit, we measured skin bleeding times in animals given orally a specific PAF-receptor antagonist L-652,731. One hour after the administration of L-652,731 (20 or 40 mg/kg), a significant prolongation of bleeding time was observed. Parameters known to interfere with the process of primary hemostasis were not altered by PAF-receptor antagonist. In addition, no changes were observed in platelet count and vessel wall arachidonic acid metabolism, as revealed by serum thromboxane B2 levels, vascular 6-ketoprostaglandin F1 alpha generation, and by aspirin experiment. The fact that aspirin alone did not induce prolongation of bleeding time in rabbits is probably due to the simultaneous inhibition of platelet thromboxane A2 and vascular prostacyclin. [3H]PAF binding to washed platelets of rabbits given L-652,731 showed a significant reduction in maximum number of detectable binding sites in comparison with values found in the same animals before the L-652,731 administration. The results suggest that the bleeding-time prolongation observed after L-652,731 administration results from its ability to selectively inhibit PAF bioactivity. Thus locally released PAF appears to exert a physiological role in the process of platelet plug formation that follows a skin incision in the rabbit.
Livio
M
M
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Vigano
G
G
Morigi
M
M
Ubiali
A
A
Galbusera
M
M
Remuzzi
G
G
D000818:Animals; D005663:Furans / Q000494:pharmacology*; D006400:Hematocrit; D006487:Hemostasis / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D010974:Platelet Aggregation; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins; D011453:Prostaglandins / Q000096:biosynthesis / Q000097:blood; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled
D005663:Furans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011453:Prostaglandins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran