title: Involvement of 5-HT1B receptors in triptan-induced contractile responses in guinea-pig isolated iliac artery.
abstract: Using a series of triptans we characterized in vitro the 5-hydroxytryptamine (5-HT) receptor that mediates the contraction in guinea-pig iliac arteries moderately precontracted by prostaglandin F2alpha (PGF2alpha). Additionally, we investigated by reverse-transcriptase polymerase chain reaction (RT-PCR) which triptan-sensitive receptor is present in this tissue. Frovatriptan, zolmitriptan, rizatriptan, naratriptan, sumatriptan, and almotriptan contracted guinea-pig iliac arteries with pD2 values of 7.52+/-0.04, 6.72+/-0.03, 6.38+/-0.06, 6.22+/-0.05, 5.86+/-0.05 and 5.26+/-0.04 respectively. For comparison, the pD2 values for 5-HT and 5-carboxamidotryptamine (5-CT) were 7.52+/-0.02 and 7.55+/-0.03 respectively. In contrast to all other triptans tested, the concentration-response curve for eletriptan was biphasic (first phase: 0.01-3 microM, pD2 approximately 6.6; second phase: > or = 10 microM). Contractions to 5-HT, 5-CT, frovatriptan, zolmitriptan, rizatriptan, naratriptan, sumatriptan, almotriptan, and eletriptan (first phase) were antagonized by the 5-HT1B/1D receptor antagonist GR127935 (10 nM) and the 5-HT1B receptor antagonist SB216641 (10 nM). RT-PCR studies in guinea-pig iliac arteries showed a strong signal for the 5-HT1B receptor while expression of 5-HT1D and 5-HT1F receptors was not detected in any sample. The present results demonstrate that triptan-induced contraction in guinea-pig iliac arteries is mediated by the 5-HT1B receptor. The guinea-pig iliac artery may be used as a convenient in vitro model to study the (cardio)vascular side-effect potential of anti-migraine drugs of the triptan family.
authors.affiliation: Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195, (Dahlem), Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jähnichen
authors.forename: O A
authors.initials: OA
authors.lastname: Radtke
authors.forename: H H
authors.initials: HH
authors.lastname: Pertz
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005544:Forecasting; D006168:Guinea Pigs; D007083:Iliac Artery / Q000187:drug effects* / Q000473:pathology* / Q000601:surgery; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology; D023303:Oxazolidinones / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists; D018170:Sumatriptan / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014363:Tryptamines
chemical_list: D001549:Benzamides; D002227:Carbazoles; D007211:Indoles; C108531:N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; D010069:Oxadiazoles; D023303:Oxazolidinones; D010879:Piperazines; D010880:Piperidines; D011759:Pyrrolidines; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D058829:Serotonin 5-HT1 Receptor Antagonists; D014230:Triazoles; D014363:Tryptamines; C409045:almotriptan; C115647:eletriptan; C089750:zolmitriptan; C090701:GR 127935; D012701:Serotonin; C093622:rizatriptan; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D007650:Ketanserin; D015237:Dinoprost; C108128:frovatriptan; C106783:naratriptan