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Titolo:
THE SELECTIVE 5-HT1A ANTAGONIST RADIOLIGAND [H-3] WAY-100635 LABELS BOTH G-PROTEIN-COUPLED AND FREE 5-HT1A RECEPTORS IN RAT-BRAIN MEMBRANES
Autore:
GOZLAN H; THIBAULT S; LAPORTE AM; LIMA L; HAMON M;
Indirizzi:
UNIV PARIS 06,INSERM,U288,91 BLVD HOP F-75634 PARIS 13 FRANCE UNIV PARIS 06,INSERM,U288 F-75634 PARIS 13 FRANCE
Titolo Testata:
European journal of pharmacology. Molecular pharmacology section
fascicolo: 2, volume: 288, anno: 1995,
pagine: 173 - 186
SICI:
0922-4106(1995)288:2<173:TS5AR[>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
BINDING-SITES; 5-HYDROXYTRYPTAMINE1A RECEPTORS; REGULATORY PROTEINS; 5-HT(1A) RECEPTORS; INVITRO BINDING; SUBTYPES; AGONIST; POTENT; AUTORADIOGRAPHY; IDENTIFICATION;
Keywords:
5-HT1A RECEPTOR; G-PROTEIN; 5-HT1A RECEPTOR ANTAGONIST; AUTORADIOGRAPHY, QUANTITATIVE; [H-3] 8-OH-DPAT ([H-3]8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN); [H-3] WAY 100635;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
H. Gozlan et al., "THE SELECTIVE 5-HT1A ANTAGONIST RADIOLIGAND [H-3] WAY-100635 LABELS BOTH G-PROTEIN-COUPLED AND FREE 5-HT1A RECEPTORS IN RAT-BRAIN MEMBRANES", European journal of pharmacology. Molecular pharmacology section, 288(2), 1995, pp. 173-186

Abstract

The tritiated derivative of the novel silent 5-HT1A receptor antagonist WAY 100635 ethoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide] was tested as a potential radioligand of 5-HT1A receptors in the rat brain. Binding assays with membranes from various brain regions showed that [H-3]WAY 100635 specifically bound to a homogeneous population of sites, with a K-d of 0.10 nM. The regional distribution of [H-3]WAY 100635 specific binding sites, as assessed in membrane binding assays and by autoradiography of labelled brain sections, superimposed exactly over that of 5-HT1A receptors specifically labelled by [H-3]8-hydroxy-2-(di-n-propylamino)tetralin ([H-3]8-OH-DPAT). Furthermore, the positive correlation (r = 0.96) between the respective pK(i) values of a large series of ligands as inhibitors of the specific binding of [H-3]WAY 100635 and [H-3]8-OH-DPAT in hippocampal membranes indicated that their pharmacological properties were similar. Nevertheless, marked differences also existed between [H-3]8-OH-DPAT and [H-3]WAY 100635 specific binding, as the former was inhibited by 1-100 mu M GTP and GppNHp, whereas the latter was enhanced by these guanine nucleotides. In contrast, Mn2+ (1-10 mM) increased the specific bindingof [H-3]8-OH-DPAT, but inhibited that of [H-3]WAY 100635. Treatment of membranes with N-ethylmaleimide (1-5 mM) markedly reduced their capacity to specifically bind [H-3]8-OH-DPAT, but slightly increased (at 1mM) or did not affect (at 5 mM) their [H-3]WAY 100635 specific binding capacity. Finally, the B-max of [H-3]WAY 100635 specific binding sites was regularly 50-60% higher than that of [H-3]8-OH-DPAT in the samemembrane preparations from various brain regions (hippocampus, septum, cerebral cortex). These data are compatible with the idea that whereas [H-3]8-OH-DPAT only binds to G-protein-coupled 5-HT1A receptors, [H-3]WAY 100635 is a high affinity ligand of both G-protein-coupled and free 5-HT1A receptor binding subunits in brain membranes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 21:48:30