Sequence and functional analysis of cloned guinea pig and rat serotonin 5-HT1D receptors: common pharmacological features within the 5-HT1D receptor subfamily.
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.
Wurch
T
T
Laboratory of Cellular and Molecular Neurobiology, Centre de Recherche Pierre Fabre, Castres, France.
Palmier
C
C
Colpaert
F C
FC
Pauwels
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D004285:Dogs; D006168:Guinea Pigs / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D051381:Rats / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism*
D008024:Ligands; D011985:Receptors, Serotonin; D000242:Cyclic AMP