The canine external carotid vasoconstrictor 5-HT1 receptor: blockade by 5-HT1B (SB224289), but not by 5-HT1D (BRL15572) receptor antagonists.
In vagosympathectomised dogs pre-treated intravenously (i.v.) with mesulergine (300 microg/kg), 1-min intracarotid (i.c.) infusions of 5-hydroxytryptamine (5-HT; 0.3-30 microg/min) and sumatriptan (1-30 microg/min) dose-dependently decreased external carotid blood flow, without affecting mean blood pressure or heart rate. Treatment with the selective 5-HT1B receptor antagonist SB224289 (2,3,6,7-tetrahydro-1'-methyl-5-[2'-methyl-4'(5-methyl-1,2,4-oxadiazo l-3-yl) biphenyl-4-carbonyl]furo[2,3f]indole-3-spiro-4'-piperidine hydrochloride; 30-300 microg/kg, i.v.) produced a potent, specific and dose-dependent blockade of this response, whereas the selective 5-HT1D receptor antagonist BRL15572 (1-(3-chlorophenyl)-4-[3,3-diphenyl(2-(S,R) hydroxypropanyl)piperazine]hydrochloride; 30-300 microg/kg, i.v.) was ineffective. It is concluded that mainly 5-HT1B, but not 5-HT1D receptors mediate the canine external carotid vasoconstriction by 5-HT and sumatriptan.
De Vries
P
P
Department of Pharmacology, Cardiovascular Research Institute COEUR, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Sánchez-López
A
A
Centurión
D
D
Heiligers
J P
JP
Saxena
P R
PR
Villalón
C M
CM
D000758:Anesthesia; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002342:Carotid Artery, External / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004873:Ergolines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D010881:Piperidones / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology; D013562:Sympathectomy; D014628:Vagotomy; D014661:Vasoconstriction / Q000502:physiology*
D001713:Biphenyl Compounds; D004873:Ergolines; D010879:Piperazines; D010881:Piperidones; D011985:Receptors, Serotonin; C108518:SB 22489G; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D012701:Serotonin; D018170:Sumatriptan; C108532:BRL 15572; C031649:mesulergine; D009638:Norepinephrine