Proaggregatory and inhibitory effects of 2-O-ethyl analogues of platelet-activating factor (PAF) on human and rabbit platelets.
A series of 8 analogues of platelet-activating factor (PAF) in which both the acetyl group and the polar head are changed, were tested for biological activities on human and rabbit platelets in plasma. Two of these compounds, 1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid-5'-trimethylammoniumpentyl ester and 1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid-6'-trimethylammoniumhexyl ester inhibit selectively the PAF-induced aggregation response without showing any agonistic activity. Schild analysis revealed a competitive antagonism and KB values of 4.4 and 10.5 mumol/l, respectively. These results point to a crucial role of the distance between the phosphoryl group and the polar head for expression of PAF-antagonistic properties. Moreover, the substituent at the 2-position was found to influence predominantly the agonistic behaviour.
Hofmann
B
B
Institut für Pathologische Biochemie, Medizinische Akademie, Erfurt, GDR.
Ostermann
G
G
Kertscher
H P
HP
Till
U
U
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D010743:Phospholipids / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D011817:Rabbits; D013045:Species Specificity
D010743:Phospholipids; D010972:Platelet Activating Factor