OXYTOCIN INHIBITS THE UPTAKE OF SEROTONIN INTO UTERINE MAST-CELLS

Citation
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
Citations number
32
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00223565
Volume
287
Issue
1
Year of publication
1998
Pages
389 - 394
Database
ISI
SICI code
0022-3565(1998)287:1<389:OITUOS>2.0.ZU;2-5
Abstract
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.