Evidence for platelet-activating factor receptor subtypes on human polymorphonuclear leukocyte membranes

Tricia D. LeVan, Sean B. Dow, Peter B. Chase, John W. Bloom, John W. Regan, Eve Cunningham, Marilyn Halonen

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Platelet-activating factor (PAF) is a potent phospholipid mediator that acts through specific cell surface receptors. The existence of PAF receptor subtypes has been suggested by functional and radioligand binding studies in a variety of cells and tissues. This report addresses this issue more diretly and demonstrates differences between specific PAF receptors in human polymorphonuclear leukocytes (PMNs) and COS-7 cells transfected with the cloned human PAF receptor gene. The presence of more than one receptor in human PMNs is supported by three different studies. First, the K(d) from the saturation isotherms for the binding of [3H]WEB 2086 on PMNs was 7-fold larger (K(d) = 29.2 nM) than the kinetic K(d) (4.2 nM). Second, the pseudo-Hill slope determined from the saturation experiments with PMNs was significantly lower than unity (0.69 ± 0.05 SEM), and the saturation K(d) values for transfected COS-7 (K(d) = 9.6 nM) and PMN membranes were significantly different. These results contrasted with those for the transfected COS-7 cells, which showed a K(d) from the saturation isotherms similar to that of the kinetic K(d) (3.2 nM) and a pseudo-Hill slope that was not different from 1.0. Third, when the radiolabeled ligand [3H]WEB 2086 was increased in concentration from 10 to 50 nM in inhibition experiments wit the human PMN membranes, the K(i) increased, indicative of binding mainly to receptors with lower affinity. These results suggest that PAF receptor subtypes exist in human PMNs based on distinct radioligand binding characteristics from the human cloned PAF receptor.

Original languageEnglish (US)
Pages (from-to)1007-1012
Number of pages6
JournalBiochemical Pharmacology
Volume54
Issue number9
DOIs
StatePublished - Nov 1 1997

Keywords

  • G-protein coupled receptor
  • Platelet-activating factor
  • Polymorphonuclear leukocytes
  • Radioligand binding

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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