The uptake of serotonin (5HT) into mouse uterine horns, the localization of sites at which this amine could be stored and the effect of oxytocin on 5HT uptake were studied. To analyze the characteristics of the 5HT uptake process, the tissue was incubated with [3H]serotonin. The uptake of [3H]5HT was Na+ dependent and saturable (Kmapp: 166 +/- 15 nM, Vmax: 404 +/- 25 fmol/mg tissue, 30 min (diestrous); and Km: 165 +/- 39 nM, Vmax: 276 +/- 43 fmol/mg tissue, 30 min (estrous), n = 6), and was inhibited by imipramine, fluoxetine and 6-nitroquipazine (IC50: 2; 0.09 and 0.5 nM, respectively). In the myometrium the main 5HT uptake process was localized in uterine mast cells. This was determined by treating the uterine horns with 6-hydroxydopamine, by using an immunocytochemical approach and by studying the outflow of 3H under the action of stimuli directed to either mast cells (compound 48/80: 10 microgram/ml) or sympathetic nerves (high K+: 100 mM and veratridine: 20 microM) in uterine preparations. Oxytocin inhibited [3H]5HT uptake into uterine mast cells during estrus, but not in ovarectomized mice treated with progesterone. Maximal inhibition was attained at 0.03 nM, with a significant reduction in both Kmapp and Vmax (87 +/- 15 nM and 184 +/- 36 fmol/mg tissue/30 min, n = 3, respectively). This effect was reversed by the addition of OVT16, an oxytocin antagonist, at a concentration of 4 nM (Kmapp 158 +/- 35 nM, Vmax: 278 +/- 24 fmol/mg tissue, 30 min, n = 3). These findings support a new potential role of oxytocin and mast cells as a local regulators of serotonin bioavailability in myometrium. Because serotonin is recognized as an important endogenous uterotonic compound, this effect could be considered as an indirect action of oxytocin that may contribute to its potency as a labor inducer after genomic effects of estrogens are expressed in uterine tissue.