Objective. The aim of this study was to investigate the ability of serotonin to increase contractions in human myometrium. Methods. Isometric tension measurements were used to determine the effect of increasing doses of serotonin on strips of human myometrium obtained at the time of cesarean section. Results. Serotonin had little or no effect on the spontaneous activity of myometrium strips in control conditions. In tissue where this activity had been reduced by either forskolin or diazoxide, serotonin caused a dose-dependent increase in contractions and produced up to a 3-fold increase in contractions over basal activity. Conclusions.The ability of serotonin to increase contractions in the uterus appears to depend on the background activity of the tissue and is greatest in quiescent tissue. It is therefore possible that in quiescent, preterm myometrium, aberrant serotonin signaling could contribute to preterm labor. Serotonin may also play a key role in the postpartum prevention of uterine atony and consequent hemorrhage.
Hoyer D., Hannon JP, Martin GRMolecular, pharmacological and functional diversity of 5-HT receptors . Pharmacol Biochem Behav. 2002;71:533-554.
2.
Alexander SP , Mathie A., Peters JAGuide to receptors and channels, 2nd edition. Br J Pharmacol.2006 ;147(suppl 3):S1-S168.
3.
Barnes NM, Sharp T.A review of central 5-HT receptors and their function. Neuropharmacology . 1999;38:1083-1152.
4.
Kaumann AJ, Levy FO5-hydroxytryptamine receptors in the human cardiovascular system. Pharmacol Ther. 2006;111:674-706.
5.
De Ponti F.Pharmacology of serotonin: what a clinician should know. Gut. 2004;53:1520-1535.
6.
Freyburger WA , Graham BE, Rapport MM, et al. The pharmacology of 5-hydroxytryptamine (serotonin). J Pharmacol Exp Ther. 1952;105:80-86.
7.
Woolley DWA probable mechanism of action of serotonin. Proc Natl Acad Sci U S A. 1958;44:197-201.
8.
Contractor SF , Jones JJ, Lee J., Morris NFThe responses of the human myometrium to 5-hydroxytryptamine (5-HT) and oxytocin (syntocinon) and its monoamine oxidase (MAO) activity during gestation. J Physiol.1968;195:16P-17P.
9.
Minosyan TY, Lu R., Eghbali M., Toro L., Stefani E.Increased 5-HT contractile response in late pregnant rat myometrium is associated with a higher density of 5-HT2A receptors. J Physiol. 2007;581:91-97.
10.
Kelly CR, Sharif NAPharmacological evidence for a functional serotonin-2B receptor in a human uterine smooth muscle cell line. J Pharmacol Exp Ther . 2006;317:1254-1261.
11.
Sweeney G., Templeton A., Clayton RA, et al. Contractile responses to sumatriptan in isolated bovine pulmonary artery rings: relationship to tone and cyclic nucleotide levels. J Cardiovasc Pharmacol. 1995;26:751-760.
12.
Shaw AM, Bunton DC, Brown T., Irvine J., MacDonald A.Regulation of sensitivity to 5-hydroxytryptamine in pulmonary supernumerary but not conventional arteries by a 5-HT1D-like receptor. Eur J Pharmacol. 2000;408:69-80.
13.
Bardou M., Cortijo J., Loustalot C., et al. Pharmacological and biochemical study on the effects of selective phosphodiesterase inhibitors on human term myometrium. Naunyn Schmiedebergs Arch Pharmacol. 1999;360:457-463.
14.
Zawadzki W. , Zieba D., Dejneka J.Changes in uterus myoelectrical activity under influence of serotonin in sheep sensitised and non-sensitised with stilboestrol . Electr J Pol Agric Univ Vet Med. 1999;2:1-8.
15.
Cruz MA, Gonzalez C., Acevedo CG, Sepulveda WH, Rudolph MIEffects of histamine and serotonin on the contractility of isolated pregnant and non-pregnant human myometrium. Gynecol Obstet Invest. 1989;28:1-4.
16.
Rudolph MI, Rojas IG, Penissi ABUterine mast cells: a new hypothesis to understand how we are born . Biocell. 2004;28:1-11.
17.
Garfield RE , Irani AM, Scwartz LB, Bytautiene E., Romero R.Structural and functional comparison of mast cells in the pregnant versus nonpregnant human uterus. Am J Obstet Gynecol. 2006;194:261-267.
18.
Rudolph MI, Reinicke K., Cruz MA, Gallardo V., Gonzalez C., Bardisa L.Distribution of mast cells and the effect of their mediators on contractility in human myometrium. Br J Obstet Gynaecol. 1993;100:1125-1130.
19.
Bytautiene E.,Vedernikov YP, Saade GR, Romero R., Garfield REDegranulation of uterine mast cell modifies contractility of isolated myometrium from pregnant women. Am J Obstet Gynecol. 2004;191:1705-1710.
20.
Rudolph MI, Oviedo C.,Vega E., et al. Oxytocin inhibits the uptake of serotonin into uterine mast cells. J Pharmacol Exp Ther. 1998;287:389-394.
21.
Elovitz MA, Ascher-Landsberg J.,Saunders T., Phillippe M.The mechanisms underlying the stimulatory effects of thrombin on myometrial smooth muscle. Am J Gynecol. 2000;183:674-681.
22.
Adebiyi A., Adaikan GP, Prasad RNOxytocic activity of thrombin: modulation of thrombin-induced gravid rat myometrial contractions by 5-hydroxytryptamine receptor antagonists. J Perinat Med. 2004;32:126-131.
23.
Hollingsworth M., Edwards D., Miller M.Ergometrine-a partial agonist at 5-HT receptors in the uterus isolated from oestrogen-primed rat . Eur J Pharm . 1988;158:79-84.
24.
McLaughlin ADThe action of ergometrine on the isolated human uterus. J Pharm Exp Ther. 1938;64:243-249.
25.
Roberts RE, Kendall DA,Wilson VGA study of NPY-mediated contractions of the porcine ear artery. Br J Pharm. 1999; 127:284-290.
26.
Roberts RE, Tomlinson AE, Kendall DA, Wilson VGα2-Adrenoceptor-mediated contractions of the porcine isolated ear artery: evidence for a cyclic AMP-dependent and a cyclic-AMP-independent mechanism . Br J Pharm. 1998;124:1107-1114.
27.
Komalavilas P. , Mehta S., Wingard CJ, et al. PI3-kinase/Akt modulates vascular smooth muscle tone via cAMP signaling pathways. J Appl Physiol . 2001;91:1819-1827.
28.
Leroy MJ, Lugnier C., Merezek J., et al. Isolation and characterization of the rolipram-sensitive cyclic AMP-specific phosphodiesterase (type IV PDE) in human term myometrium. Cell Signal. 1994;6:405-412.
29.
Shum JKS , Melendez JA, Jeffrey JJSerotonin-induced MMP-13 production is mediated via phospholipase C, protein kinase C and ERK1/2 in rat uterine smooth muscle cells. J Biol Chem. 2002;277:42830-42840.
30.
Kordowska J. , Huang R., Wang CLPhosphorylation of caldesmon during smooth muscle contraction and cell migration or proliferation. J Biomed Sci. 2006;13:159-172.
31.
CordeauxY., Missfelder-Lobos H., Charnock-Jones DS, Smith GCS.Functional and molecular characterization of 5-HT2 serotonin receptors in myometrium from pregnant women at term. Reprod Sci.2007;14(suppl):229A.
