Specific binding of 3H-ICI 198,615, a potent LTD4 antagonist, to guinea pig cardiac ventricular membranes

Prostaglandins. 1990 Mar;39(3):241-58. doi: 10.1016/0090-6980(90)90044-v.


Peptido-leukotrienes (LTs) elicit myocardial depression in several mammalian species, and radioligand binding assays with 3H-LTC4 and 3H-LTD4 have provided evidence of putative receptor sites on guinea pig cardiac ventricular membranes (GPCVM). Our objective was to characterize specific binding of 3H-ICI 198,615, a potent and selective LTD4 antagonist, to the 155,000 X g pellet of GPCVM. 3H-ICI 198,615 (0.01-3.8 nM) showed high specific binding (85-90% of total), which was protein dependent, saturable (Bmax = 4914 +/- 706 fmol/mg protein, n = 3), of high affinity (Kd = 4.3 +/- 0.8 nM, n = 3) and without cooperativity. Equilibrium binding was achieved by 20 minutes and could be rapidly reversed by addition of excess unlabeled ICI 198,615 or FPL55712. Competition studies with 3H-ICI 198,615 against several LTD4 antagonists produced an order of potency: ICI 198,615 much greater than SKF102922 greater than FPL55712 greater than or equal to LY171883. Addition of divalent cations caused a concentration dependent decrease in specific binding apparently due to a reduction in affinity. Binding was not influenced by the guanine nucleotide analogs GTP gamma S and Gpp(NH)p, EDTA, or a multitude of diverse non-LT receptor agonists and antagonists. These data provide evidence supporting the existence of specific and high affinity binding sites for 3H-ICI 198,615 in GPCVM.

MeSH terms

  • Animals
  • Cations, Divalent / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Indazoles / metabolism*
  • Kinetics
  • Myocardium / metabolism*
  • Pyrazoles / metabolism*
  • Radioligand Assay
  • Receptors, Immunologic / metabolism*
  • Receptors, Leukotriene
  • SRS-A / antagonists & inhibitors*


  • Cations, Divalent
  • Indazoles
  • Pyrazoles
  • Receptors, Immunologic
  • Receptors, Leukotriene
  • SRS-A
  • ICI 198615