Radioligand binding of antagonists of platelet-activating factor to intact human platelets

FEBS Lett. 1988 Feb 15;228(2):285-9. doi: 10.1016/0014-5793(88)80017-6.

Abstract

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.

MeSH terms

  • Azepines / metabolism*
  • Binding Sites
  • Binding, Competitive
  • Blood Platelets / metabolism*
  • Humans
  • Kinetics
  • Platelet Activating Factor / antagonists & inhibitors
  • Platelet Activating Factor / metabolism
  • Pyridines / metabolism*
  • Thiazoles / metabolism*
  • Triazines / metabolism*
  • Triazoles*
  • Tritium

Substances

  • Azepines
  • Platelet Activating Factor
  • Pyridines
  • Thiazoles
  • Triazines
  • Triazoles
  • Tritium
  • WEB 2086
  • N-(3-chlorophenyl)-3-(3-pyridinyl)-1H,3H-pyrrolo(1,2-c)thiazole-7-carboxamide