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Contractile 5-HT1D Receptors in Human Brain Vessels

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Serotonin: Molecular Biology, Receptors and Functional Effects

Summary

The receptor which mediates the contraction elicited by 5-hydroxytryptamine (5-HT, serotonin) in human pial arterioles has been characterized. The overall rank order of agonist potency was 5-carboxamidotryptamine (5-CT) > 5-HT > RU 24969 = α-CH3-5-HT = methysergide ≫ MDL 72832 = 2-CH3-5-HT ≫ 8-OH-DPAT, with maximal contractile responses being comparable for most agonists. An excellent correlation was obtained for the vascular potencies of agonists and their published affinities for rat cortical 5-HT1B (r = 0.86; p < 0.01) and human caudate 5-HT1D (r = 0.98; p < 0.005) binding sites. The 5-HT-induced contraction was not blocked by 5-HT 1B (propranolol), 5-HT1C (mesulergine, mianserin), 5-HT2 (ketanserin, mianserin, MDL 72832) or 5-HT3 (MDL 72222) antagonists. In contrast, methiothepin (non-selective 5-HT1-like/5-HT2) and metergoline (non-selective 5-HT1D) were potent inhibitors of this vasomotor effect with respective pA2 values on the order of 8.51 and 7.06. A correlation analysis between the overall agonist/antagonist vascular potencies and their reported potencies for 5-HT-mediated second messenger effects; i.e. adenylate cyclase activity (5-HT1A, 5-HT1B or 5-HT1D-coupled effect) or inositol phosphate metabolism (5HT1C-mediated response), showed a positive correlation for 5-HT1B (r = 0.89; p < 0.001) and 5-HT1D (r = 0.90; p < 0.001) functional receptors. Our study suggests that a 5-HT1-like receptor, most likely of the 5-HT1D subtype, mediates the vasoconstriction to 5-HT in human brain vessels.

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Authors and Affiliations

  1. Laboratory of Cerebrovascular Research, Montreal Neurological Institute, 3801 University St., Montréal, Canada, H3A 2B4

    E. Hamel & D. Bouchard

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  1. E. Hamel
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  2. D. Bouchard
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Editors and Affiliations

  1. Preclinical Research, Sandoz Pharma Ltd., P.O. Box 6, CH-4002, Basel, Switzerland

    John R. Fozard

  2. Institute of Pharmacology, Erasmus University Rotterdam, P.O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands

    Pramod R. Saxena

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© 1991 Birkhäuser Verlag Basel/Switzerland

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Hamel, E., Bouchard, D. (1991). Contractile 5-HT1D Receptors in Human Brain Vessels. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_24

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  • DOI: https://doi.org/10.1007/978-3-0348-7259-1_24

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-7261-4

  • Online ISBN: 978-3-0348-7259-1

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