Investigation of the role of 5-HT1B and 5-HT1D receptors in the sumatriptan-induced constriction of porcine carotid arteriovenous anastomoses.
1. It has previously been shown that the antimigraine drug sumatriptan constricts porcine carotid arteriovenous anastomoses via 5-HT1-like receptors, identical to 5-H1B/1D receptors. The recent availability of silent antagonists selective for the 5-HT1B (SB224289) and 5-HT1D (BRL15572) receptor led us to further analyse the nature of receptors involved. 2. In pentobarbitone-anaesthetized, bilaterally vagosympathectomized pigs, sumatriptan (30, 100 and 300 microg kg(-1), i.v.) dose-dependently decreased carotid arteriovenous anastomotic conductance by up to 70+/-5%. 3. The dose-related decreases in carotid arteriovenous anastomotic conductance by sumatriptan (30, 100 and 300 microg kg(-1), i.v.) remained unchanged in animals treated (i.v.) with 1 mg kg(-1) of BRL15572 (maximum decrease: 72+/-3%), but were significantly attenuated by 1 mg kg(-1) (maximum decrease: 30+/-11%) and abolished by 3 mg kg(-1) (maximum decrease: 3+/-7%) of SB224289. The highest dose of SB224289 did not attenuate the hypertension, tachycardia or increases in carotid blood flow induced by bolus injections of noradrenaline (0.1-3 microg kg(-1), i.v.). 4. The results indicate that sumatriptan constricts porcine carotid arteriovenous anastomoses primarily via 5-HT1B, but not via 5-HT1D receptors.
De Vries
P
P
Department of Pharmacology, Dutch Migraine Research Group and Cardoivascular Research Institute, COEUR, Erasmus University Medical Centre Rotterdam, The Netherlands.
Willems
E W
EW
Heiligers
J P
JP
Villalón
C M
CM
Saxena
P R
PR
D000818:Animals; D001163:Arteriovenous Anastomosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology; D018170:Sumatriptan / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013552:Swine; D013562:Sympathectomy; D014628:Vagotomy; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001713:Biphenyl Compounds; D010879:Piperazines; D010881:Piperidones; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; C108518:SB 22489G; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D014662:Vasoconstrictor Agents; D018170:Sumatriptan; C108532:BRL 15572