Radioligand binding of antagonists of platelet-activating factor to intact human platelets.
Two new antagonists of platelet-activating factor (PAF), the pyrrolothiazole derivative 52770 RP and the triazolodiazepine WEB 2086, have been studied as radioligands in intact human platelets. [3H]52770 RP and [3H]WEB 2086 bound specifically to high-affinity sites with dissociation constants (Kd) of 14.8 and 6.1 nM, respectively. The maximal number of sites for [3H]52770 RP binding was approx. 15-fold higher than for [3H]PAF and [3H]WEB 2086. In addition, C16-PAF, lyso-PAF, WEB 2086 and 52770 RP had Ki values which were nearly identical for both [3H]PAF and [3H]WEB 2086, whereas only 52770 RP competed for [3H]52770 RP-binding sites. These results demonstrate that in human platelets the sites of [3H]WEB 2086 binding are identical to [3H]PAF-binding sites, whereas those of [3H]52770 RP are not. [3H]WEB 2086 appears, therefore, to be a suitable antagonist radioligand for labelling PAF receptors.
Ukena
D
D
Department of Thoracic Medicine, Brompton Hospital, London, England.
Dent
G
G
Birke
F W
FW
Robaut
C
C
Sybrecht
G W
GW
Barnes
P J
PJ
D001381:Azepines / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism*; D014227:Triazines / Q000378:metabolism*; D014230:Triazoles; D014316:Tritium
D001381:Azepines; D010972:Platelet Activating Factor; D011725:Pyridines; D013844:Thiazoles; D014227:Triazines; D014230:Triazoles; D014316:Tritium; C052518:WEB 2086; C053706:N-(3-chlorophenyl)-3-(3-pyridinyl)-1H,3H-pyrrolo(1,2-c)thiazole-7-carboxamide