Investigation of the role of 5‐HT1B and 5‐HT1D receptors in the sumatriptan‐induced constriction of porcine carotid arteriovenous anastomoses

• Published in: British journal of pharmacology Vol. 127; no. 2; pp. 405 - 412
• Main Authors: De Vries, Peter, Willems, Edwin W, Heiligers, Jan P C, Villalón, Carlos M, Saxena, Pramod R
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.1999; Nature Publishing
• Subjects: 5‐HT1B/1D receptors; Animals; arteriovenous anastomoses; Arteriovenous Anastomosis - drug effects; Biological and medical sciences; Biphenyl Compounds - pharmacology; BRL15572; Cardiovascular system; Carotid Arteries - drug effects; carotid blood flow; Dose-Response Relationship, Drug; In Vitro Techniques; Medical sciences; migraine; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Pharmacology. Drug treatments; pig; Piperazines - pharmacology; Piperidones - pharmacology; Receptor, Serotonin, 5-HT1B; Receptor, Serotonin, 5-HT1D; Receptors, Serotonin - drug effects; SB224289; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Spiro Compounds - pharmacology; sumatriptan; Sumatriptan - antagonists & inhibitors; Sumatriptan - pharmacology; Swine; Sympathectomy; Vagotomy; Vasoconstrictor Agents - antagonists & inhibitors; Vasoconstrictor Agents - pharmacology; Vasodilator agents. Cerebral vasodilators; Agonist; Intravenous administration; Sumatriptan; Antimigrainous agent; Arteriovenous anastomosis; 5-HT1 Serotonine receptor; Serotonin agonist; Pig; Vertebrata; Mammalia; Animal; Artiodactyla; Circulatory system; Mechanism of action; Ungulata
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702572

It has previously been shown that the antimigraine drug sumatriptan constricts porcine carotid arteriovenous anastomoses via 5‐HT1‐like receptors, identical to 5‐HT1B/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. In pentobarbitone‐anaesthetized, bilaterally vagosympathectomized pigs, sumatriptan (30, 100 and 300 μg kg−1, i.v.) dose‐dependently decreased carotid arteriovenous anastomotic conductance by up to 70±5%. The dose‐related decreases in carotid arteriovenous anastomotic conductance by sumatriptan (30, 100 and 300 μg 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 μg kg−1, i.v.). The results indicate that sumatriptan constricts porcine carotid arteriovenous anastomoses primarily via 5‐HT1B, but not via 5‐HT1D receptors. British Journal of Pharmacology (1999) 127, 405–412; doi:10.1038/sj.bjp.0702572