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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Contractile 5-HT1B receptors in human cerebral arteries: pharmacological characterization and localization with immunocytochemistry.

1 The cerebrovascular receptor(s) that mediates 5-hydroxytryptamine (5-HT)-induced vasoconstriction in human cerebral arteries (HCA)has proven difficult to characterize, yet these are essential in migraine. We have examined 5-HT receptor subtype distribution in cerebral blood vessels by immunocytochemistry with antibodies selective for human 5-HT1B and human 5-HT1D receptors and also studied the contractile effects of a range of 5-HT receptor agonists and antagonists in HCA. 2 Immunocytochemistry of cerebral arteries showed dense 5-HT1B receptor immunoreactivity (but no 5-HT1D receptor immunoreactivity) within the smooth muscle wall of the HCA. The endothelial cell layer was well preserved and weak 5-HT1B receptor immunoreactivity was present. 3 Pharmacological experiments on HCA with intact endothelium showed that 5-carboxamidotryptamine was significantly more potent than alpha-methyl-5-HT, 2-methyl-5-HT and 5-HT in causing vasoconstriction. The 5-HT1B/1D receptor agonists naratriptan, sumatriptan, zolmitriptan and 181C91 (N-desmethyl zolmitriptan), all induced equally strong contractions and with similar potency as 5-HT. The maximum contractile response was significantly less for avitriptan and dihydroergotamine. There was a significant correlation between vasoconstrictor potency and 5-HT1B- and 5-HT1D-receptor affinity, but not with 5-HT1A-, 5-ht1F or 5-HT2- receptor affinity. 4 The 5-HT1B/1D-receptor antagonist GR 55562 (10-7 - 10-6 M) inhibited the contractile responses to sumatriptan and 5-CT in a competitive manner with a pKB value for GR 55562 of 7. 4. Furthermore, ketanserin (10-7 M), prazosin (10-7 M), and sulpiride (10-7 M) were devoid of significant antagonistic activity of 5-HT-induced contraction in the HCA. 5 The results are compatible with the hypothesis that the 5-HT1B receptors play a major role in 5-HT-induced vasoconstriction in HCA.[1]


  1. Contractile 5-HT1B receptors in human cerebral arteries: pharmacological characterization and localization with immunocytochemistry. Nilsson, T., Longmore, J., Shaw, D., Olesen, I.J., Edvinsson, L. Br. J. Pharmacol. (1999) [Pubmed]
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