The GR127935‐sensitive 5‐HT1 receptors mediating canine internal carotid vasoconstriction: resemblance to the 5‐HT1B, but not to the 5‐HT1D or 5‐ht1F, receptor subtype

• Published in: British journal of pharmacology Vol. 132; no. 5; pp. 991 - 998
• Main Authors: Centurión, David, Sánchez‐López, Araceli, De Vries, Peter, Saxena, Pramod R, Villalón, Carlos M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2001; Nature Publishing
• Subjects: 5‐HT1B receptor; 5‐Hydroxytryptamine (5‐HT); Biological and medical sciences; Blood vessels and receptors; BRL15572; Fundamental and applied biological sciences. Psychology; internal carotid vasoconstriction; LY344864; PNU‐142633; ritanserin; SB224289; Vertebrates: cardiovascular system; Fissipedia; Carnivora; Agonist; Molecular form; Sympathectomy; Serotonin; Sumatriptan; Vasoconstriction; Smooth muscle; 5-HT1 Serotonine receptor; Muscle contraction; Artery; Vertebrata; Mammalia; Animal; Carotid; Dog
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703913

This study has further investigated the pharmacological profile of the GR127935‐sensitive 5‐HT1 receptors mediating vasoconstriction in the internal carotid bed of anaesthetized vagosympathectomized dogs. One‐minute intracarotid infusions of the agonists 5‐hydroxytryptamine (5‐HT; 0.1–10 μg min−1; endogenous ligand) and sumatriptan (0.3–10 μg min−1; 5‐HT1B/1D), but not PNU‐142633 (1–1000 μg min−1; 5‐HT1D) or LY344864 (1–1000 μg min−1; 5‐ht1F), produced dose‐dependent decreases in internal carotid blood flow without changing blood pressure or heart rate. The responses to 5‐HT were apparently resistant to blockade by i.v. administration of the antagonists SB224289 (300 μg kg−1; 5‐HT1B), BRL15572 (300 μg kg−1; 5‐HT1D) or ritanserin (100 μg kg−1; 5‐HT2). In contrast, the responses to sumatriptan were antagonized by SB224289, but not by BRL15572. In the animals receiving SB224289, but not those receiving BRL15572, the subsequent administration of ritanserin abolished the 5‐HT‐induced vasoconstriction and unmasked a vasodilator component. Similarly, in ritanserin‐treated animals, the subsequent administration of SB224289, but not BRL15572, completely blocked the 5‐HT‐induced vasoconstriction, revealing vasodilatation. In animals receiving initially BRL15572, the subsequent administration of SB224289 did not affect (except at 10 μg min−1) the vasoconstrictor responses to 5‐HT. Notably, in animals pretreated with 1000 μg kg−1 of mesulergine, a 5‐HT2/7 receptor antagonist, 5‐HT produced a dose‐dependent vasoconstriction, which was practically abolished by SB224289. After BRL15572, no further blockade was produced and the subsequent administration of ritanserin was similarly inactive. These results suggest that the GR127935‐sensitive 5‐HT1 receptors mediating canine internal carotid vasoconstriction resemble the 5‐HT1B but not the 5‐HT1D or 5‐ht1F, receptor subtype. British Journal of Pharmacology (2001) 132, 991–998; doi:10.1038/sj.bjp.0703913