5-HT1-like receptor-mediated contraction in the human internal mammary artery.
We wished to characterize the 5-hydroxytryptamine (5-HT) receptors mediating vasoconstriction in the human internal mammary artery (IMA). Segments of the IMA obtained from patients undergoing coronary by-pass surgery were suspended in an organ bath and exposed to 5-HT and sumatriptan (SUM), a 5-HT1-like receptor agonist, in the presence and absence of potassium chloride (KCl) and angiotensin II. 5-HT induced concentration-dependent contractions in all quiescent and pre-contracted preparations. SUM induced small contractions in 70% of quiescent IMA rings, whereas it elicited marked and concentration-dependent contractions in all of the preparations given a moderate tone by a threshold concentration of KCl and angiotensin II. The efficacy of SUM was higher in precontracted arteries. Concentration-effect curves (CEC) of 5-HT and SUM were not affected by the 5-HT3-receptor antagonist tropisetron (1 microM). The nonselective antagonist, methiothepin (30 nM), shifted the CEC of SUM to the right. 5-HT2A-receptor antagonist, ketanserin (1 microM) inhibited responses to 5-HT, whereas it affected only the responses to the smaller concentrations of SUM. When methiothepin (30 nM) was applied in the presence of ketanserin (1 microM), a further inhibition in the responses to 5-HT was observed. These results suggest that 5-HT1-like receptors mediate the contractile action of SUM and contribute to that of 5-HT in IMA.
Yildiz
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O
Department of Pharmacology, GATA Gülhane Faculty of Medicine, Ankara, Turkey.
Ciçek
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S
Ay
I
I
Tatar
H
H
Tuncer
M
M
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D008719:Methiothepin / Q000494:pharmacology; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D012701:Serotonin; D008719:Methiothepin; D018170:Sumatriptan; D007650:Ketanserin