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The GR127935‐sensitive 5‐HT 1 receptors mediating canine internal carotid vasoconstriction: resemblance to the 5‐HT 1B , but not to the 5‐HT 1D or 5‐ht 1F , receptor subtype
Author(s) -
Centurión David,
SánchezLópez Araceli,
De Vries Peter,
Saxena Pramod R,
Villalón Carlos M
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703913
Subject(s) - 5 ht receptor , vasoconstriction , receptor , serotonin , chemistry , medicine
This study has further investigated the pharmacological profile of the GR127935‐sensitive 5‐HT 1 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‐HT 1B/1D ), but not PNU‐142633 (1–1000 μg min −1 ; 5‐HT 1D ) or LY344864 (1–1000 μg min −1 ; 5‐ht 1F ), 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‐HT 1B ), BRL15572 (300 μg kg −1 ; 5‐HT 1D ) or ritanserin (100 μg kg −1 ; 5‐HT 2 ). 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‐HT 2/7 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‐HT 1 receptors mediating canine internal carotid vasoconstriction resemble the 5‐HT 1B but not the 5‐HT 1D or 5‐ht 1F , receptor subtype.British Journal of Pharmacology (2001) 132 , 991–998; doi: 10.1038/sj.bjp.0703913