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Investigation of the role of 5‐HT 1B and 5‐HT 1D receptors in the sumatriptan‐induced constriction of porcine carotid arteriovenous anastomoses
Author(s) -
De Vries Peter,
Willems Edwin W,
Heiligers Jan P C,
Villalón Carlos M,
Saxena Pramod R
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702572
Subject(s) - sumatriptan , arteriovenous anastomosis , receptor , medicine , constriction , anastomosis , 5 ht receptor , anesthesia , endocrinology , pharmacology , chemistry , serotonin , surgery , agonist
It has previously been shown that the antimigraine drug sumatriptan constricts porcine carotid arteriovenous anastomoses via 5‐HT 1 ‐like receptors, identical to 5‐HT 1B/1D receptors. The recent availability of silent antagonists selective for the 5‐HT 1B (SB224289) and 5‐HT 1D (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‐HT 1B , but not via 5‐HT 1D receptors.British Journal of Pharmacology (1999) 127 , 405–412; doi: 10.1038/sj.bjp.0702572