Sequence and Functional Analysis of Cloned Guinea Pig and Rat Serotonin 5-HT1D Receptors: Common Pharmacological Features Within the 5-HT1D Receptor Subfamily
Autor: | Francis Colpaert, Christiane Palmier, Thierry Wurch, Petrus J. Pauwels |
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Rok vydání: | 2002 |
Předmět: |
Agonist
Ketanserin medicine.drug_class Guinea Pigs Molecular Sequence Data Ritanserin Biology Ligands Biochemistry Guinea pig Mice Cellular and Molecular Neuroscience Dogs Cyclic AMP medicine Animals Humans Amino Acid Sequence Receptor Molecular biology Rats Receptors Serotonin COS Cells 5-HT1 receptor Rabbits Serotonin 5-HT1D receptor medicine.drug |
Zdroj: | Journal of Neurochemistry. 68:410-418 |
ISSN: | 1471-4159 0022-3042 |
Popis: | This study was undertaken to investigate the pharmacology of cloned guinea pig and rat 5-hydroxytryptamine (serotonin; 5-HT)1D receptor sites. Guinea pig, rat, and mouse 5-HT1D receptor genes were cloned, and their amino acid sequences were compared with those of the human, dog, and rabbit. The overall amino acid sequence identity between these 5-HT1D receptors is high and varies between 86 and 99%. The sequence homology is slightly more divergent (13-27%) in the N-terminal extracellular region of these 5-HT1D receptors. Guinea pig and rat 5-HT1D receptors, stably and separately expressed in rat C6 glial cells, are negatively coupled to cyclic AMP formation upon stimulation with agonists, as previously found for cloned human 5-HT1D receptor sites. The cyclic AMP data show some common pharmacological features for the 5-HT1D receptors of guinea pig, rat, and human: an almost similar rank order of potency for the investigated 5-HT1D receptor agonists, stereoselectivity for the binding affinity and agonist potency of R(+)-8-hydroxy-2-(di-n-propylamino)tetralin, and equal 5-HT1D receptor-mediated antagonist potency for methiothepin and the 5-HT2 receptor antagonists ritanserin and ketanserin. In conclusion, the pharmacology of the cloned 5-HT1D receptor subtype seems, unlike the 5-HT1B receptor subtype, conserved among various mammal species such as the human, guinea pig, and rat. |
Databáze: | OpenAIRE |
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