The Presence of Leukotriene C4- and Prostacyclin-Binding Sites in Nonpregnant Human Uterine Tissue

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Abstract
Human uterine tissue can synthesize leukotrienes and prostacyclin (PGI2) from arachidonic acid via the lipoxygenase and cyclooxygenase pathways, respectively. Leukotriene C4 stimulates myometrial and vascular smooth muscle contractions, whereas PGI2 inhibits them. In addition, these eicosanoids have other actions in uterine tissue. All of these actions are possibly mediated by specific receptors, but such receptors have not been demonstrated in human uterine tissue. Therefore, these quantitative light microscopic autoradiographic studies were undertaken to determine whether nonpregnant human uterine tissue contains specific leukotriene C4- and PGI2-binding sites. Studies with [3H]leukotriene C4 indicated that luminal epithelial cells of the endometrium, stromal cells, elongated and circular myometrial smooth muscle, and arteriolar smooth muscle contained numerous binding sites. Glandular epithelium, vascular endothelium, and erythrocytes, on the other hand, contained few or no leukotriene C4-binding sites. The number of binding sites in luminal epithelial cells of the endometrium was as high as that in lung, which is a rich source of these binding sites. The number of binding sites in these epithelial cells was higher (P < 0.05) than that in stromal cells, circular myometrial smooth muscle and arteriolar smooth muscle, but there were no significant (P > 0.05) differences among the other cells. Maximal binding occurred at 5 min of incubation at 22 or 38 C. The presence of serine borate, a .gamma.-glutamyl transpeptidase inhibitor, in the incubation medium resulted in a small to moderate increase in leukotriene C4 binding to uterine cells. Binding to the cells was significantly (P < 0.001) reduced after coincubation with excess unlabeled leukotriene C4, but not with excess unlabeled leukotriene A4, leukotriene B4, leukotriene D4, leukotriene E4, prostaglandin (PG)E1, PGF2.alpha. or PGI2. Studies with [3H]PGI2 demonstrated that while myometrium and vascular smooth muscle contained PGI2-specific binding sites, endometrium and vascular endothelium contained very few or no binding sites. Elongated myometrial smooth muscle contained a higher number of binding sites than circular myometrial smooth muscle and vascular smooth muscle (P < 0.01). PGI2 binding to the uterine cells was dependent on the time and temperature of incubation, and Ca2+ was not required for binding. Coincubation with unlabeled PGI2, but not with its stable metabolite 6-keto-PGF1a, resulted in a significant reduction (P < 0.001) of binding to uterine cells. PGE2, PGF2.alpha., and leukotriene C4 also had no effect on [3H]PGI2 binding. In conclusion, we demonstrated the presence of specific leukotriene C4- and PGI2-binding sites in nonpregnant human uterine tissue. Their presence in different uterine cell types suggests that leukotriene C4 may regulate both contractile and noncontractile functions, whereas PGI2 may regulate only contractile functions of the nonpregnant human uterine tissue.