Pharmacological study of the effects of leukotrienes C4, D4, E4 & F4 on guinea pig trachealis: interaction with FPL-55712.
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.
D000818:Animals; D002867:Chromones / Q000494:pharmacology*; D006168:Guinea Pigs; D017999:Leukotriene E4; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D013189:SRS-A / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*
D002867:Chromones; D013189:SRS-A; D017999:Leukotriene E4; C037113:leukotriene F-4; C006312:FPL 55712