Evidence for 5-HT(1B/1D) and 5-HT(2A) receptors mediating constriction of the canine internal carotid circulation.
The present study has investigated the preliminary pharmacological profile of the receptors mediating vasoconstriction to 5-hydroxytryptamine (5-HT) in the internal carotid bed of vagosympathectomised dogs. One minute intracarotid infusions of the agonists 5-HT (0.1 - 10 microg min(-1)), sumatriptan (0.3 - 10 microg min(-1); 5-HT(1B/1D)), 5-methoxytryptamine (1 - 100 microg min(-1); 5-HT(1), 5-HT(2), 5-HT(4), 5-ht(6) and 5-HT(7)) or DOI (0.31 - 10 microg min(-1); 5-HT(2)), but not 5-carboxamidotryptamine (0.01 - 0.3 microg min(-1); 5-HT(1), 5-ht(5A) and 5-HT(7)), 1-(m-chlorophenyl)-biguanide (mCPBG; 1 - 1000 microg min(-1); 5-HT(3)) or cisapride (1 - 1000 microg min(-1); 5-HT(4)), resulted in dose-dependent decreases in internal carotid blood flow, without changing blood pressure or heart rate. The vasoconstrictor responses to 5-HT, which remained unaffected after saline, were resistant to blockade by i.v. administration of the antagonists ritanserin (100 microg kg(-1); 5-HT(2A/2B/2C)) in combination with tropisetron (3000 microg kg(-1); 5-HT(3/4)) or the cyclo-oxygenase inhibitor, indomethacin (5000 microg kg(-1)), but were abolished by the 5-HT(1B/1D) receptor antagonist, GR127935 (30 microg kg(-1)). Interestingly, after administration of GR127935, the subsequent administration of ritanserin unmasked a dose-dependent vasodilator component. GR127935 or saline did not practically modify the vasoconstrictor effects of 5-MeO-T. In animals receiving GR127935, the subsequent administration of ritanserin abolished the vasoconstrictor responses to 5-MeO-T unmasking a dose-dependent vasodilator component. The vasoconstriction induced by sumatriptan was antagonized by GR127935, but not by ritanserin. Furthermore, ritanserin (100 microg kg(-1)) or ketanserin (100 microg kg(-1); 5-HT(2A)), but not GR127935, abolished DOI-induced vasoconstrictor responses. The above results suggest that 5-HT-induced internal carotid vasoconstriction is predominantly mediated by 5-HT(1B/1D) and 5-HT(2A) receptors.
Departamento de Farmacobiología, CINVESTAV-IPN, Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México D.F., México.
D
D
Centurión
M I
MI
Ortiz
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; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D044402:Receptor, Serotonin, 5-HT2A; 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*
D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin