Involvement of lipoxygenase products in myometrial contractions

Studies with an in situ preparation of guinea pig uterus suggest the possible involvement of the lipoxygenase pathway of arachidonic acid (AA) metabolism in myometrial contractions. Female guinea pigs were sensitized to ovalbumin (OA) on day one of their estrous cycle. On day 14, these pigs were anesthetized and the uterus was cannulated for measuring contractions. OA challenge, with histamine antagonism (methapyrilene) resulted in uterine contractions which significantly raised myometrial tonus, presumably due to AA metabolites. Pretreatment with high doses of indomethacin resulted in only 60% inhibition of the OA induced contraction, suggesting the remaining contraction was due to something other than cyclooxygenase products. In the presence of indomethacin and methapyrilene, the addition of AA to increase available substrate caused increased myometrial tone following antigen challenge. This increase in uterine tone was inhibited in a dose dependent fashion by FPL-55712 demonstrating that leukotrienes can contract the uterus and that antigen challenge may provide a means for studying leukotriene involvement in uterine pathophysiology.