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Involvement of 5-HT1B receptors in triptan-induced contractile responses in guinea-pig isolated iliac artery

  • S. Jähnichen
  • O. A. Radtke
  • H. H. Pertz
Original Article

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 F (PGF). 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 μM, pD2≈6.6; second phase: ≥10 μM). 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.

Keywords

Guinea-pig 5-HT receptors Iliac artery Migraine Serotonin Triptans Vasoconstriction 

Notes

Acknowledgements

The authors wish to thank Professor Schunack for financial support of the study. The generous gifts of drugs by the pharmaceutical companies mentioned in Materials and methods are gratefully acknowledged.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Institut für PharmazieFreie Universität BerlinBerlin (Dahlem)Germany

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