Species-dependent differences of high affinity [3H]PAF-binding to platelets from humans and pigs and its inhibition by selected antagonists.
The sensitivity of blood platelets towards PAF (1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine) strongly varies with species and is primarily responsible for different pathophysiological effects after its administration to experimental animals. Platelets from domestic pigs were shown to possess one single class of high-affinity PAF-binding sites. Receptor density and sensitivity of pig platelets towards PAF were distinctly higher than those from humans. Preincubation of platelets from both species with PAF-specific antagonists diminished the high affinity [3H]PAF-binding concentration-dependently. Eight PAF-related antagonists, the ginkgolide BN 52021, as well as the hetrazepine WEB 2086 were included and mean inhibitory concentrations (IC50) between 0.09 and 124 mumol/l ascertained. Comparing the rank order of inhibitory potency considerable differences became evident between both species. The quotients of the IC50 values obtained with human and pig platelets differed for about two orders of magnitude. Moreover, the inhibitory profile of the PAF-related antagonists was found to be highly sensitive to small structural changes. Based on these findings a species-dependent difference at the PAF receptor level of platelets from pigs and humans is suggested.
Ostermann
G
G
Institut für Pathologische Biochemie, Medizinische Akademie Erfurt, F.R.G.
Lorenz
A
A
Hofmann
B
B
Kertscher
H P
HP
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D004224:Diterpenes; D046934:Ginkgolides; D006801:Humans; D007783:Lactones; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D013045:Species Specificity; D013552:Swine; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; C045856:ginkgolide B