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

Abstract Leukotrienes D 4 ⩾ C 4 > E 4 ⩾ F 4 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 × 10 −6 M) competitive antagonist of LTC 4 , LTE 4 and LTF 4 (slope not significantly different from one). The interaction of FPL-55712 with LTD 4 may be noncompetitive (slope B ) indicated that FPL-55712 was more effective at blocking LTE 4 and LTF 4 compared to LTC 4 and LTD 4 . In the presence of higher concentrations of FPL-55712 (1.9 × 10 −5 M) the antagonism of LTC 4 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.