Human isolated coronary artery contraction to sumatriptan characterised by the selective 5-HT1B/1D receptor antagonist GR55562.
The antimigraine drug, sumatriptan, contracts the human coronary artery both in vivo and in vitro. Because sumatriptan has been associated with cardiac side effects, it is important to characterise the receptor involved in sumatriptan-induced coronary artery contraction. Using the agonists sumatriptan and 5-carboxamidotryptamine and the selective 5-HT1B/1D receptor antagonist GR55562, we have investigated the involvement of 5-HT1B/1D receptors in the contraction of the human isolated coronary artery. Contractions to sumatriptan (pEC50: 6.1+/-0.2, maximal effect: 21+/-4% of 100 mM K+-induced contraction) were competitively antagonised by GR55562. The pA2 of GR55562 (7.40+/-0.16) was in accord with its reported affinity at the human 5-HT1B receptor. Since the contractions to 5-carboxamidotryptamine did not reach a maximum with the highest concentration used (10 microM), pEC50 values could not be calculated for Schild analysis. However, using the pEC10%/K+ values (negative logarithm of the concentration needed to induce 10% of the contraction to 100 mM K+), GR55562 proved a less potent antagonist against 5-carboxamidotryptamine than against sumatriptan. These results show that sumatriptan contracts the human isolated coronary artery via 5-HT1B/1D receptors, most probably the 5-HT1B subtype. 5-Carboxamidotryptamine may contract the human isolated coronary artery, at least partly, via a novel yet to be characterised, receptor.
Maassen VanDenBrink
A
A
Department of Pharmacology, Erasmus University Medical Center Rotterdam EMCR, The Netherlands.
Reekers
M
M
Bax
W A
WA
Saxena
P R
PR
D001549:Benzamides / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D001549:Benzamides; C470302:HTR1B protein, human; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; C103477:3-(3-(dimethylamino)propyl)-4-hydroxy-N-(4-(4-pyridinyl)phenyl)benzamide; D012701:Serotonin; D013373:Substance P; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D015237:Dinoprost; D011188:Potassium