Cysteinyl leukotrienes C4, D4 and E4 elicited concentration-dependent contractile response of pregnant and non-pregnant pig uterine strips during incubation in De Jalon solution in concentrations between 1 x 10(-9)M and 1 x 10(-5)M for LTC4 and LTD4, and between 1 x 10(-8)M and 1 x 10(-5)M for LTE4. The maximum contractions elicited by leukotrienes were 77.5 +/- 3.0%, 86.0 +/- 2.6% and 37.5 +/- 2.5% of these elicited by histamine 1 x 10(-5)M for LTC4, LTD4 and LTE4, respectively. FPL 55712, leukotriene end-organ antagonist, antagonized the uterine contractile response to cysteinyl leukotrienes in dose-dependent manner. Indomethacin, an inhibitor of cyclooxygenase pathway of arachidonic acid metabolism also antagonized leukotriene-induced contractions of pig uterus. Pregnant uteri were more susceptible to leukotriene action than non-pregnant uteri, and response increased parallelly with advancement of pregnancy. These results demonstrate that LTC4, LTD4 and LTE4 possess significant uterine contractile activity in domestic pig, which may partially be mediated indirectly via cyclooxygenase products of arachidonic acid metabolism.
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