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-HT( 2A) and 5HT(1B/D) agonists contracts HUA. The 5-HT-induced contractions were fully inhibited by ketanserin (5-HT(2A) antagonist). The 5-HT( 7)-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-HT(2A)- and 5-HT(1B/1D)-activation lead to vasoconstriction and 5-HT(7)-activation induces vasorelaxation. Concerning histamine receptors, H(1)-activation induces contraction and H(2)- and H(3)-activation lead to vasorelaxation.
CICS-Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, Covilhã, Portugal.
António José
AJ
Santos-Silva
Elisa
E
Cairrão
Bruno
B
Marques
Ignacio
I
Verde
D000242:Cyclic AMP / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D011968:Receptors, Histamine / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014469:Umbilical Arteries / Q000187:drug effects / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D018492:Dopamine Antagonists; D017442:Histamine Agonists; D006633:Histamine Antagonists; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D044402:Receptor, Serotonin, 5-HT2A; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000242:Cyclic AMP