Comparison of antagonist and agonist binding to the leukotriene B4 receptor intact human polymorphonuclear neutrophils (PMN)

J Pharmacol Exp Ther. 1992 Jul;262(1):80-9.


In the present studies, the pharmacology of the leukotriene B4 (LTB4) receptor on intact human polymorphonuclear neutrophils (PMN) was characterized using radioligand binding techniques with [3H]LTB4 and a novel LTB4 receptor antagonist radioligand [3H]CGS 23131 (LY223982). Saturation studies revealed that [3H]CGS 23131 labeled a single class of recognition sites with high affinity (Kd = 13 nM) and limited capacity (apparent Bmax = 2.8 pmol/10(7) cells). In contrast, [3H]LTB4 labeled both a set of high (Kd = 0.3 nM) and lower affinity (Kd = 5 nM) recognition sites. However, the apparent density of [3H]LTB4 binding to intact human PMN (combined Bmax = 380 fmol/10(7) cells) was approximately 14% of that observed with [3H]CGS 23131. In ligand competition studies, various LTB4 agonists and antagonists were found to inhibit the binding of [3H]CGS 23131, revealing a pharmacological profile consistent with the specific labeling of the LTB4 receptor. A positive rank order correlation (r = 0.79) was observed between the ligand competition profiles obtained with [3H]CGS 23131 and [3H]LTB4. Both LTB4 and its omega oxidation product, 20-OH-LTB4, were found to inhibit the binding of 1.0 nM [3H]CGS 23131 in a biphasic fashion consistent with the existence of multiple affinity components of the LTB4 receptor. In competing for 0.5 nM [3H]LTB4 binding, these compounds were found to produce monophasic inhibition curves, which was indicative of a selective interaction at the high-affinity LTB4 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study

MeSH terms

  • Benzophenones / chemical synthesis
  • Benzophenones / metabolism*
  • Benzophenones / pharmacology
  • Binding, Competitive
  • Drug Interactions
  • Humans
  • Leukotriene B4 / antagonists & inhibitors*
  • Leukotrienes / metabolism
  • Leukotrienes / pharmacology
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / metabolism*
  • Receptors, Leukotriene B4


  • Benzophenones
  • Leukotrienes
  • Receptors, Immunologic
  • Receptors, Leukotriene B4
  • LY 223982
  • Leukotriene B4