Characterization of the human basilar artery contractile response to 5-HT and triptans.
To study the contractile responses of the human basilar artery to 5-hydroxytryptamine (5-HT), sumatriptan, zolmitriptan and naratriptan, and to characterize the 5-HT receptor subtypes involved on those responses, human basilar artery rings were prepared for isometric contraction, protein isolation and Western blotting analysis. Concentration-response (CR) curves were made for all agonists in the absence or in the presence of selective antagonists at 5-HT1B (cyanopindolol), 5-HT1D (BRL 15,572) and 5-HT2 (ketanserin) receptors. We also used anti-5-HT1B and 5-HT1D receptor antibodies to search for the expression of protein of these receptor subtypes. From the CR curves, the relative intrinsic activity and potency of these agonists were determined. The ranking order for the intrinsic activity was 5-HT > or = sumatriptan > zolmitriptan > or = naratriptan, whereas that for the potency was zolmitriptan > or = 5-HT > or = sumatriptan > naratriptan. Our results also show that the human basilar artery seems to have a mixed population of 5-HT1B/1D receptors mediating the contractile response to triptans, which is also suggested by the expression of both receptor subtypes. There is also a population of 5-HT2 receptors for which the antimigraine drugs used have no apparent affinity. From this study, one can conclude that the second generation triptans have lower contractile capacity than sumatriptan, suggesting that they have a better cerebrovascular safety profile.
Silva
Sónia A
SA
Laboratório de Farmacologia, Faculdade de Farmácia, Universidade de Coimbra, Largo D. Dinis, 3000-141 Coimbra, Portugal. sonias@ci.uc.pt
Marques
Francisco B
FB
Fontes Ribeiro
Carlos A
CA
D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D023303:Oxazolidinones; D010880:Piperidines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D014662:Vasoconstrictor Agents; C089750:zolmitriptan; D012701:Serotonin; D018170:Sumatriptan; C106783:naratriptan