Abstract
We studied the role of several serotonin (5-HT) and histamine receptors in the regulation of human umbilical artery (HUA) contractility. Among the 5-HT agonists used, only the 5-HT 2A and 5HT1B/D agonists contracts HUA. The 5-HT-induced contractions were fully inhibited by ketanserin (5-HT2A antagonist). The 5-HT 7-activation also relaxes and increases intracellular cyclic adenosine monophosphate (cAMP). Among the histamine receptor agonists, only betahistine (H1 agonist) induced significant contractile effect. Histamine-induced contraction was partially relaxed by pyrilamine (H1 antagonist). Betahistine-induced contraction was partially blocked by dimaprit (H 2 agonist) and by the H3 agonist when a low concentration of forskolin is present. Both, H2 and H3 agonists increased the cAMP intracellular levels in HUA smooth muscle. These findings show that in HUA, 5-HT2A- and 5-HT1B/1D-activation lead to vasoconstriction and 5-HT7-activation induces vasorelaxation. Concerning histamine receptors, H1-activation induces contraction and H2- and H3-activation lead to vasorelaxation.
Similar content being viewed by others
References
Tufan H, Ayan-Polat B, Tecder-Unal M, Polat G, Kayhan Z, Ogus E. Contractile responses of the human umbilical artery to KCl and serotonin in Ca-free medium and the effects of levcromakalim. Life Sci. 2003;72(12):1321–1329.
Leung SW, Quan A, Lao TT, Man RY. Efficacy of different vasodilators on human umbilical arterial smooth muscle under normal and reduced oxygen conditions. Early Hum Dev. 2006;82(7):457–462.
Karlsson C, Bodelsson G, Bodelsson M, Stjernquist M. Characterization of5-hydroxytryptamine receptors mediating circular smooth muscle contraction in the human umbilical artery. Gynecol Obstet Invest. 1999;47(2):102–107.
Quan A, Leung SW, Lao TT, Man RY. 5-hydroxytryptamine and thromboxane A2 as physiologic mediators of human umbilical artery closure. J Soc Gynecol Investig. 2003;10(8):490–495.
Santos-Silva AJ, Cairrão E, Morgado M, Álvarez E, Verde I. PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteries. Eur J Pharmacol. 2008;582(1–3):102–109.
Cairrao E, Alvarez E, Santos-Silva AJ, Verde I. Potassium channels are involved in testosterone-induced vasorelaxation of human umbilical artery. Naunyn Schmiedebergs Arch Pharmacol. 2008;376(5):375–383.
Mitchell RG, Porter JF. Histamine and granulocytes in the umbilical cord blood of infants at birth. Br J Pharmacol. 1970;40(2):310–316.
Taniguchi K. Vasospastic action of serotonin on the umbilical artery in normal and preeclamptic patients. J Obstet Gynaecol. 1995;21(1):37–42.
Bolte AC, van Geijn HP, Dekker GA. Pathophysiology of preeclampsia and the role of serotonin. Eur J Obstet Gynecol Reprod Biol. 2001;95(1):12–21.
Brew O, Sullivan MH. The links between maternal histamine levels and complications of human pregnancy. J Reprod Immunol. 2006;72(1–2):94–107.
Feinberg BB. Preeclampsia: the death of Goliath. Am J Reprod Immunol. 2006;55(2):84–98.
Gupta S, Hanff LM, Visser W, et al. Functional reactivity of 5-HT receptors in human umbilical cord and maternal subcutaneous fat arteries after normotensive or pre-eclamptic pregnancy. J Hypertens. 2006;24(7):1345–1353.
Nagai S, Tsurumaki T, Abe H, Higuchi H. Functional serotonin and histamine receptor subtypes in porcine ciliary artery in comparison with middle cerebral artery. Eur J Pharmacol. 2007;570(1–3):159–166.
Ullmer C, Schmuck K, Kalkman HO, Lubbert H. Expression of serotonin receptor mRNAs in blood vessels. FEBS Lett. 1995;370(3):215–221.
Pauwels PJ. Diverse signalling by 5-hydroxytryptamine (5-HT) receptors. Biochem Pharmacol. 2000;60(12):1743–1750.
Villalon CM, Centurion D. Cardiovascular responses produced by 5-hydroxytriptamine:a pharmacological update on the receptors/mechanisms involved and therapeutic implications. Naunyn. Schmiedebergs Arch Pharmacol. 2007;376(1–2):45–63.
Lovren F, Li XF, Lytton J, Triggle C. Functional characterization and m-RNA expression of 5-HT receptors mediating contraction in human umbilical artery. Br J Pharmacol. 1999;127(5):1247–1255.
Jahnichen S, Glusa E, Pertz HH. Evidence for 5-HT2B and 5-HT7 receptor-mediated relaxation in pulmonary arteries of weaned pigs. Naunyn Schmiedebergs Arch Pharmacol. 2005;371(1):89–98.
Leurs R, Smit MJ, Timmerman H. Molecular pharmacological aspects of histamine receptors. Pharmacol Ther. 1995;66(3):413–463.
Hill SJ, Ganellin CR, Timmerman H, et al. International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev. 1997;49(3):253–278.
Lovenberg TW, Roland BL, Wilson SJ, et al. Cloning and functional expression of the human histamine H3 receptor. Mol Pharmacol. 1999;55(6):1101–1107.
Levi R, Smith NC. Histamine H(3)-receptors: a new frontier in myocardial ischemia. J Pharmacol. Exp Ther. 2000;292(3):825–830.
Martinez AC, Rivera L, Raposo R, Garcia-Sacristan A, Benedito S. Evidence of histamine receptor function in isolated horse penile dorsal arteries. Life Sci. 2000;67(11):1355–1368.
Obuchowicz R, Pawlik MW, Brzozowski T, Konturek SJ, Pawlik WW. Involvement of central and peripheral histamine H(3) receptors in the control of the vascular tone and oxygen uptake in the mesenteric circulation of the rat. J Physiol Pharmacol. 2004;55(1 pt 2):255–267.
de Esch IJ, Thurmond RL, Jongejan A, Leurs R. The histamine H4 receptor as a new therapeutic target for inflammation. Trends Pharmacol Sci. 2005;26(9):462–469.
Zhang DX, Gauthier KM, Campbell WB. Mechanisms of histamine-induced relaxation in bovine small adrenal cortical arteries. Am J Physiol. 2005;289(6):E1058–1063.
Schultheiss G, Hennig B, Schunack W, Prinz G, Diener M. Histamine-induced ion secretion across rat distal colon: involvement of histamine H1 and H2 receptors. Eur J Pharmacol. 2006;546(1–3):161–170.
Jin H, Koyama T, Hatanaka Y, Akiyama S, Takayama F, Kawasaki H. Histamine-induced vasodilation and vasoconstriction in the mesenteric resistance artery of the rat. Eur J Pharmacol. 2006;529(1–3):136–144.
Fiscus RR, Dyer DC. Effects of indomethacin on contractility of isolated human umbilical artery. Pharmacology. 1982;24(6):328–336.
MacLennan SJ, Whittle MJ, McGrath JC. 5-HT1-like receptors requiring functional cyclo-oxygenase and 5-HT2 receptors independent of cyclo-oxygenase mediate contraction of the human umbilical artery. Br J Pharmacol. 1989;97(3):921–933.
Martinez AC, Novella S, Raposo R, et al. Histamine receptors in isolated bovine oviductal arteries. Eur J Pharmacol. 1997;326(2–3):163–173.
Wylam ME, Samsel RW, Schumacker PT, Umans JG. Extracellular calcium and intrinsic tone in the human umbilical artery. J Pharmacol Exp Ther. 1993;266(3):1475–1481.
Okatani Y, Wakatsuki A, Reiter RJ. Protective effect of melatonin against homocysteine-induced vasoconstriction of human umbilical artery. Biochem Biophys Res Commun. 2000;277(2):470–475.
Rogines-Velo MP, Pelorosso FG, Zold CL, et al. Characterization of 5-HT receptor subtypes mediating contraction in human umbilical vein. 1. Evidence of involvement of 5-HT2A receptors using functional and radioligand binding assays. Naunyn Schmiedebergs Arch Pharmacol. 2002;366(6):587–595.
Johnstone FD, Ugaily-Thulesius L, Thulesius O, Nasrat AN. Umbilical artery reactivity and ultrastructural changes in pregnancy-induced hypertension and other complicated pregnancies. Clin Physiol. 1987;7(6):493–502.
Verheggen R, Meier A, Werner I, et al. Functional 5-HT receptors in human occipital artery. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(4):391–401.
Cortijo J, Marti-Cabrera M, Bernabeu E, et al. Characterization of5-HT receptors on human pulmonary artery and vein: functional and binding studies. Br J Pharmacol. 1997;122(7):1455–1463.
Nilsson T, Longmore J, Shaw D, et al. Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques. Eur J Pharmacol. 1999;372(1):49–56.
Hawley J, Rubin PC, Hill SJ. Distribution of receptors mediating phosphoinositide hydrolysis in cultured human umbilical artery smooth muscle and endothelial cells. Biochem Pharmacol. 1995;49(7):1005–1011.
Daneshmand MA, Keller RS, Canver MC, Canver AC, Canver CC. Histamine H1 and H2 receptor-mediated vasoreactivity of human internal thoracic and radial arteries. Surgery. 2004;136(2):458–463.
Keitoku M, Maruyama Y, Takishima T. The receptor mechanisms for histamine actions in proximal portion differ from those in distal portion in human coronary artery. Tohoku J Exp Med. 1988;154(4):415–416.
Schneider A, Riess P, Elbers A, Neugebauer E, Schaefer U. Polyclonal anti-histamine H2 receptor antibodies detect differential expression of H2 receptor protein in primary vascular cell types. Inflamm Res. 2004;53(6):223–229.
Martinez AC, Prieto D, Raposo R, et al. Endothelium-independent relaxation induced by histamine in human dorsal penile artery. Clin Exp Pharmacol Physiol. 2000;27(7):500–507.
Suzuki Y, Saitoh M, Suzumori K, Kajikuri J, Itoh T. Characterization of changes in mechanical responses to histamine in omental resistance arteries in pre-eclampsia. Br J Pharmacol. 2000;131(1):37–42.
Cherifi Y, Pigeon C, Le Romancer M, Bado A, Reyl-Desmars F, Lewin MJ. Purification of a histamine H3 receptor negatively coupled to phosphoinositide turnover in the human gastric cell line HGT1. J Biol Chem. 1992;267(35):25315–25320.
Levi R, Seyedi N, Schaefer U, et al. Histamine H3-receptor signaling in cardiac sympathetic nerves: Identification of a novel MAPK-PLA2-COX-PGE2-EP3R pathway. Biochem Pharmacol. 2007;73(8):1146–1156.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Santos-Silva, A.J., Cairrão, E., Marques, B. et al. Regulation of Human Umbilical Artery Contractility By Different Serotonin and Histamine Receptors. Reprod. Sci. 16, 1175–1185 (2009). https://doi.org/10.1177/1933719109343787
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719109343787