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Titolo:
Cloning of serotonin 5-HT1 receptor subtypes from the chimpanzee, gorilla and Rhesus monkey and their agonist-induced guanosine 5'gamma S-35 triphosphate binding
Autore:
Alberts, GL; Pregenzer, JF; Im, WB; Slightom, JL;
Indirizzi:
Pharmacia & Upjohn Inc, Genom, Kalamazoo, MI 49007 USA Pharmacia & Upjohn Inc Kalamazoo MI USA 49007 om, Kalamazoo, MI 49007 USA
Titolo Testata:
NEUROSCIENCE LETTERS
fascicolo: 3, volume: 280, anno: 2000,
pagine: 223 - 227
SICI:
0304-3940(20000225)280:3<223:COS5RS>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-S BINDING; ADENYLATE-CYCLASE; INHIBITION; MIGRAINE;
Keywords:
5-HT1D; 5-HT1B; 5-HT1F; animal models for migraine; agonist-induced GTP gamma S-35 binding; non-human primates;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Im, WB 7251-209-512,301 Henrietta St, Kalamazoo, MI 49007 USA 7251-209-512,301 Henrietta St Kalamazoo MI USA 49007 MI 49007 USA
Citazione:
G.L. Alberts et al., "Cloning of serotonin 5-HT1 receptor subtypes from the chimpanzee, gorilla and Rhesus monkey and their agonist-induced guanosine 5'gamma S-35 triphosphate binding", NEUROSCI L, 280(3), 2000, pp. 223-227

Abstract

5-HT1 receptor subtypes ((1B), (1D) and (1F)) have been implicated in migraine pathophysiology and their ligands have been examined for pharmacological actions in various experimental animal models. Considerable divergences exist, however, in their primary sequences between experimental animals andhuman, and additional models closer to human, such as non-human primates seem to be useful for migraine research. Earlier, we cloned the 5-HT1D, and here 5-HT1B and 5-HT1F receptors from the chimpanzee, gorilla and Rhesus monkey, via polymerase chain reactions with their genomic DNAs and primers designed from the corresponding human receptors. Direct sequencing of PCR products showed that the 5-HT1B receptors from the chimpanzee, gorilla and monkey differ from the human receptor by 0, 1 and 7 residues, respectively while 5-HT1F receptors differ by 0, 3 and 10 residues, respectively. These divergent residues are mostly conservatively substituted and also largely confined to the N-terminal region and the 3rd intracellular loop, away from transmembrane segments and intracellular loops near membrane which are critical for ligand binding and G protein coupling. The chimpanzee 5-HT1D, 5-HT1B and monkey 5-HT1F receptors, as heterologously expressed in human embryonickidney 293 cells, showed robust agonist-induced guanosine 5'gamma S-35 triphosphate (GTP gamma(35)S) binding through activation of G proteins containing G gamma(i) subunits. Moreover, pronounced inhibition of basal GTP gamma(35)S binding by methiothepin (an antagonist), representing constitutively active receptors, was observed with only 5-HT1D. Overall, ligand binding and GTP gamma(35)S binding profiles for these primate receptors are comparable to those for the human receptors and validate non-human primates as useful models for human migraine research. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 07:46:10