Effects of synthetic analogues of platelet-activating factor (PAF) on fibrinolytic activity in the rat.
PAF and structural analogues were investigated for their in vivo effects on fibrinolytic activity (FA) in the rat. The i.v. administration of 1 and 4 micrograms/kg PAF caused a dose-dependent increase in FA which was shown to be attributable to the release of tissue-type plasminogen activator (t-PA). 1-O-hexadecyl-2-O-ethyl-glycero-3-phosphoric acid-2'-N-propargyl-N,N'- dimethylammoniumethyl ester (I) and 1-O-hexadecyl-2-(n-propyl)-propanediol-3-phosphocholine (II) increased FA according to their proaggregatory activity. In contrast, 1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid-5'-trimethylammoniumpentyl ester (III), a competitive antagonist of PAF, reduced the PAF induced increase of FA by 30%. Under identical conditions BN 52021 given at 1 and 10 micrograms/kg amounts diminished the effect of PAF by 47 and 77%, respectively. These results indicate that the PAF induced PA release in vivo is receptor mediated.
Hofmann
B
B
Institut für Pathologische Biochemie, Medizinische Akademie, Erfurt, GDR.
Meisgeier
U
U
Kertscher
P
P
Ostermann
G
G
D000818:Animals; D005342:Fibrinolysis / Q000187:drug effects*; D010743:Phospholipids / Q000138:chemical synthesis; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D010743:Phospholipids; D010972:Platelet Activating Factor; D010959:Tissue Plasminogen Activator