Ability of ketanserin to block different receptors in human placental vessels.
5-Hydroxytryptamine (5-HT), noradrenaline (NA) and histamine induced concentration-dependent contractions in segments of human chorionic arteries and veins, whereas clonidine, an alpha 2-adrenoceptor agonist, had no effect. 5-HT and histamine induced strong contractions, while NA elicited weak contractions in some segments. The maximal response was similar for 5-HT and histamine. The order of potency (EC50 values) was: 5-HT greater than or equal to NA greater than or equal to histamine. These agonists induced tachyphylaxis, and single concentrations caused transient contractions. Contractions elicited by 5-HT were antagonized by ketanserin, a 5-HT2-receptor antagonist, which also antagonized the responses to NA and histamine, but at greater concentrations than those needed for 5-HT responses. Contractions elicited by histamine were reduced by diphenydramine. Low concentrations of 5-HT amplified contractions caused by NA and histamine. The results indicate that: (i) 5-HT is the most potent constrictor agent tested in these vessels; (ii) its effects are mediated by 5-HT2-receptors; and (iii) ketanserin at therapeutic plasma concentrations (10(-7) M) seems to block mainly 5-HT2-receptors, and alpha 1-adrenergic- and H1-receptors to a small extent only.
Marin
J
J
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad de Extremadura, Madrid, Spain.
Reviriego
J
J
Fernandez-Alfonso
M S
MS
D005260:Female; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists; D006801:Humans; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply; D011247:Pregnancy; D011955:Receptors, Drug / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists
D006633:Histamine Antagonists; D011955:Receptors, Drug; D012702:Serotonin Antagonists; D012701:Serotonin; D006632:Histamine; D007650:Ketanserin; D009638:Norepinephrine