Mi. Rudolph et al., OXYTOCIN INHIBITS THE UPTAKE OF SEROTONIN INTO UTERINE MAST-CELLS, The Journal of pharmacology and experimental therapeutics, 287(1), 1998, pp. 389-394
The uptake of serotonin (5HT) into mouse uterine horns, the localizati
on of sites at which this amine could be stored and the effect of oxyt
ocin on 5HT uptake were studied. To analyze the characteristics of the
5HT uptake process, the tissue was incubated with [H-3]serotonin. The
uptake of [H-3]5HT was Na+ dependent and saturable (Km(app): 166 +/-
15 nM, Vmax: 404 +/- 25 fmol/mg tissue, 30 min (diestrous); and Km: 16
5 +/- 39 nM, Vmax: 276 +/- 43 fmol/mg tissue, 30 min (estrous), n = 6)
, and was inhibited by imipramine, fluoxetine and 6-nitroquipazine (IC
50: 2; 0.09 and 0.5 nM, respectively). In the myometrium the main 5HT
uptake process was localized in uterine mast cells. This was determine
d by treating the uterine horns with 6-hydroxydopamine, by using an im
munocytochemical approach and by studying the outflow of H-3 under the
action of stimuli directed to either mast cells (compound 48/80: 10 m
u g/ml) or sympathetic nerves (high K+: 100 mM and veratridine: 20 mu
M) in uterine preparations. Oxytocin inhibited [H-3]5HT uptake into ut
erine 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 Km(app) and Vmax (87 +/- 15 nM and 184 /- 36 fmol/mg tissue/30 min, n = 3, respectively). This effect was rev
ersed by the addition of OVT16, an oxytocin antagonist, at a concentra
tion of 4 nM (Km(app) 158 +/- 35 nM, Vmax: 278 +/- 24 fmol/mg tissue,
30 min, n = 3). These findings support a new potential role of oxytoci
n and mast cells as a local regulators of serotonin bioavailability in
myometrium. Because serotonin is recognized as an important endogenou
s uterotonic compound, this effect could be considered as an indirect
action of oxytocin that may contribute to its potency as a labor induc
er after genomic effects of estrogens are expressed in uterine tissue.