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http://purl.uniprot.org/citations/9225282http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9225282http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9225282http://www.w3.org/2000/01/rdf-schema#comment"The anti-migraine compound, sumatriptan, has been shown to have substantial affinity for the cloned human 5-HT1F receptor suggesting that, in addition to 5-HT1B/5-HT1D receptor subtypes, the 5-HT1F receptor may be a therapeutic target for the treatment of migraine. Several investigators have used the guinea pig plasma extravasation model to evaluate potential anti-migraine drugs. Since species differences in the pharmacology of serotonin receptors are well known, we compared the pharmacological profiles of the cloned human and guinea pig 5-HT1F receptors in order to validate the usefulness of the in vivo model in predicting anti-migraine activity of compounds targeted for humans. We have cloned the guinea pig 5-HT1F by homology to the human 5-HT1F receptor and evaluated its pharmacological profile using radioligand binding assays. The cloned guinea pig 5-HT1F gene exhibited 94% amino acid identity to the corresponding human homolog. High affinity (Kd approximately 10 nM) [3H]5-HT binding was detected to membranes obtained from Cos-7 cells transiently expressing the guinea pig 5-HT1F receptor. The cloned guinea pig receptor displayed typical 5-HT1F receptor pharmacology with the following rank order of binding affinities: 5-HT > sumatriptan > 1-NP = DHE > alpha-methyl 5-HT > metergoline > methiothepin > 5-CT. The pharmacological profiles of the cloned guinea pig and human 5-HT1F receptors were very similar as reflected by the high correlation (r2 = 0.72, slope = 0.76) observed between the binding affinities of compounds for these two species homologs. In situ hybridization studies in guinea pig tissue revealed 5-HT1F receptor mRNA expression in the neurons of the trigeminal ganglion, suggesting that the 5-HT1F receptor may play a role in the presynaptic inhibition of neuropeptide release at the level of the intracranial vasculature, thereby blocking the development of neurogenic inflammation. Dorsal root ganglion cells also moderately expressed the 5-HT1F transcripts. The localization of the 5-HT1F receptor to areas involved in the mediation and transfer of nociceptive information implies a role for this receptor in pain processing. These findings indicate that a selective 5-HT1F agonist may be a novel approach to treat migraine."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.org/dc/terms/identifier"doi:10.1016/s0028-3908(97)00020-8"xsd:string
http://purl.uniprot.org/citations/9225282http://purl.org/dc/terms/identifier"doi:10.1016/s0028-3908(97)00020-8"xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Adham N."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Adham N."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Bard J.A."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Bard J.A."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Branchek T.A."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Branchek T.A."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Durkin M.M."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Durkin M.M."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Kucharewicz S."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Kucharewicz S."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Weinshank R.L."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Weinshank R.L."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Zgombick J.M."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/author"Zgombick J.M."xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/date"1997"xsd:gYear
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/date"1997"xsd:gYear
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/name"Neuropharmacology"xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/name"Neuropharmacology"xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/pages"569-576"xsd:string
http://purl.uniprot.org/citations/9225282http://purl.uniprot.org/core/pages"569-576"xsd:string
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