Pharmacological study of the effects of leukotrienes C4, D4, E4 & F4 on guinea pig trachealis: interaction with FPL-55712

Prostaglandins. 1983 Nov;26(5):833-43. doi: 10.1016/0090-6980(83)90066-7.


Leukotrienes D4 greater than C4 greater than E4 greater than F4 produced qualitatively similar contractions of guinea-pig trachealis, which were antagonized by the SRS-antagonist FPL-55712. Schild analyses indicated that FPL-55712 when tested in a low concentration range (0.57 - 5.7 X 10(-6) M) was a competitive antagonist of LTC4, LTE4 and LTF4 (slope not significantly different from one). The interaction of FPL-55712 with LTD4 may be noncompetitive (slope less than 1). Comparison of the calculated dissociation constants (-log KB) indicated that FPL-55712 was more effective at blocking LTE4 and LTF4 compared to LTC4 and LTD4. In the presence of higher concentrations of FPL-55712 (1.9 X 10(-5) M) the antagonism of LTC4 became noncompetitive. These findings indicate that important differences exist in the interaction of FPL-55712 with the various peptido leukotrienes in guinea pig trachealis. Discovery of more selective antagonists will be needed to determine if multiple receptor subtypes are present in this tissue.

MeSH terms

  • Animals
  • Chromones / pharmacology*
  • Guinea Pigs
  • Leukotriene E4
  • Male
  • Muscle Contraction / drug effects
  • SRS-A / analogs & derivatives*
  • SRS-A / antagonists & inhibitors
  • SRS-A / pharmacology*
  • Trachea / drug effects*


  • Chromones
  • SRS-A
  • Leukotriene E4
  • leukotriene F-4
  • FPL 55712