Regulation of Human Umbilical Artery Contractility By Different Serotonin and Histamine Receptors

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-HT2A and 5HT(1B/D) agonists contracts HUA. The 5-HT-induced contractions were fully inhibited by ketanserin (5-HT2A antagonist). The 5-HT7-activation also relaxes and increases intracellular cyclic adenosine monophosphate (cAMP). Among the histamine receptor agonists, only betahistine (H-1 agonist) induced significant contractile effect. Histamine-induced contraction was partially relaxed by pyrilamine (H-1 antagonist). Betahistine-induced contraction was partially blocked by dimaprit (H-2 agonist) and by the H-3 agonist when a low concentration of forskolin is present. Both, H-2 and H-3 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, H-1-activation induces contraction and H-2-and H-3-activation lead to vasorelaxation.