PAF-agonistic and -antagonistic behaviour of new synthetic ether phospholipids. I. Studies on blood platelets in vitro.
Structural analogues of platelet-activating factor (PAF, 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine) in which the acetyl group and the polar head have been replaced by ethyl and a pyridine ring, respectively, were tested for biological activities on blood platelets in vitro. In comparison with PAF most of the analogues exerted weak pro-aggregatory effects and both structural modifications were found to contribute to the lowering of platelet-stimulating activity. 1-O-Hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid 4-(N,N-dimethylamino)-pyridinium ethylester (DMAP-ethyl-PAF) did not activate platelets but inhibited PAF-induced platelet responses. The inhibition was concentration-dependent and of competitive type. KB values for inhibiting the PAF-induced aggregation of human and rabbit platelets in plasma were 3.2 and 0.55 mumol/l, respectively. There is also evidence that the PAF-antagonistic behaviour of DMAP-ethyl-PAF is attributable to an inhibition of the binding of PAF to its putative receptor.
Ostermann
G
G
Institute of Pathological Biochemistry, Medical Academy of Erfurt, G.D.R.
Hofmann
B
B
Kertscher
H P
HP
Till
U
U
D006801:Humans; D066298:In Vitro Techniques; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C072626:1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid 4-(N,N-dimethylamino)-pyridinium ethylester; D012701:Serotonin