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.
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 microg min(-1); endogenous ligand) and sumatriptan (0.3 - 10 microg min(-1); 5-HT(1B/1D)), but not PNU-142633 (1 - 1000 microg min(-1); 5-HT(1D)) or LY344864 (1 - 1000 microg 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 microg kg(-1); 5-HT(1B)), BRL15572 (300 microg kg(-1); 5-HT(1D)) or ritanserin (100 microg 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 microg min(-1)) the vasoconstrictor responses to 5-HT. Notably, in animals pretreated with 1000 microg 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.
Departamento de Farmacobiologia, CINVESTAV-IPN, Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México D.F., México.
D
D
Centurión
A
A
Sánchez-López
P
P
De Vries
P R
PR
Saxena
C M
CM
Villalón
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002343:Carotid Artery, Internal / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D000096642:Receptor, Serotonin, 5-HT1F
D010069:Oxadiazoles; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D000096642:Receptor, Serotonin, 5-HT1F; C090701:GR 127935