Contraction of guinea pig uterus by synthetic leukotrienes

Abstract

Synthetic leukotrienes (LT) C4 and D4 elicited concentration-dependent contractions of the guinea pig uterus between 10(-8)-10(-6)M, whereas LTE4 appeared 1000-fold weaker. The potencies of LTC4 and LTD4 were similar to that of acetylcholine and PGF2 alpha but weaker than that of PGE2. The maximal contractions elicited by LTC4 and LTD4 were 66.0 +/- 2.1% and 63.8 +/- 4.6% that elicited by acetylcholine. FPL 55712 (10(-5)M) antagonized the uterine contractile activity of LTD4, while meclofenamic acid at 10(-5)M but not at 10(-6)M also antagonized the LTD4-induced contraction. Radioimmunoassay of the uterine tissue bathing fluid following LTD4 indicated the variable presence of low concentrations of PGE2, PGF2 alpha and TxB2. These results demonstrate that LTC4 and LTD4 possess significant uterine contractile activity, which may only partially be mediated indirectly via prostaglandin products.