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Sequence and Functional Analysis of Cloned Guinea Pig and Rat Serotonin 5‐HT 1D Receptors: Common Pharmacological Features Within the 5‐HT 1D Receptor Subfamily
Author(s) -
Wurch Thierry,
Palmier Christiane,
Colpaert Francis C.,
Pauwels Petrus J.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68010410.x
Subject(s) - serotonin , 5 ht receptor , subfamily , receptor , guinea pig , biology , serotonin antagonists , endocrinology , genetics , gene
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‐HT 1D 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‐HT 1D 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‐HT 1D receptors. Guinea pig and rat 5‐HT 1D 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‐HT 1D receptor sites. The cyclic AMP data show some common pharmacological features for the 5‐HT 1D receptors of guinea pig, rat, and human: an almost similar rank order of potency for the investigated 5‐HT 1D receptor agonists, stereoselectivity for the binding affinity and agonist potency of R (+)‐8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin, and equal 5‐HT 1D receptor‐mediated antagonist potency for methiothepin and the 5‐HT 2 receptor antagonists ritanserin and ketanserin. In conclusion, the pharmacology of the cloned 5‐HT 1D receptor subtype seems, unlike the 5‐HT 1B receptor subtype, conserved among various mammal species such as the human, guinea pig, and rat.