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Titolo:
Antidepressants enhance glucocorticoid receptor function in vitro by modulating the membrane steroid transporters
Autore:
Pariante, CM; Makoff, A; Lovestone, S; Feroli, S; Heyden, A; Miller, AH; Kerwin, RW;
Indirizzi:
Univ London Kings Coll, Inst Psychiat, Sect Clin Neuropharmacol, London SE5 8AF, England Univ London Kings Coll London England SE5 8AF l, London SE5 8AF, England Univ London Kings Coll, Inst Psychiat, Dept Neurosci, London SE5 8AF, England Univ London Kings Coll London England SE5 8AF i, London SE5 8AF, England Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 ychiat & Behav Sci, Atlanta, GA 30322 USA
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 6, volume: 134, anno: 2001,
pagine: 1335 - 1343
SICI:
0007-1188(200111)134:6<1335:AEGRFI>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; MESSENGER-RNA; GENE-EXPRESSION; IN-VIVO; AMITRIPTYLINE; BINDING; CELLS; DEXAMETHASONE; DRUGS;
Keywords:
cortisol; corticosterone; dexamethasone; glucocorticoid receptor; H-89; hypothalamic-pituitary-adrenal (HPA) axis; L929 cells; multiple drug resistance (MDR) p-glycoprotein; tricyclic antidepressants; selective serotonin reuptake inhibitor (SSRI) verapamil;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Pariante, CM Univ London Kings Coll, Inst Psychiat, Sect Clin Neuropharmacol, 1 WindsorWalk,Denmark Hill, London SE5 8AF, England Univ London Kings Coll 1 Windsor Walk,Denmark Hill London England SE5 8AF
Citazione:
C.M. Pariante et al., "Antidepressants enhance glucocorticoid receptor function in vitro by modulating the membrane steroid transporters", BR J PHARM, 134(6), 2001, pp. 1335-1343

Abstract

1 Previous data demonstrate that the tricyclic antidepressant, desipramine, induces glucocorticoid receptor (GR) translocation from the cytoplasm to the nucleus in L929 cells and increases dexamethasone-induced GR-mediated gene transcription in L929 cells stably transfected with the mouse mammary tumour virus-chloramphenicol acetyltransferase (MMTV-CAT) reporter gene (LMCAT cells) (Pariante et al., 1997).2 To extend these findings, the present study has investigated the effectsof 24 h coincubation of LMCAT cells with dexamethasone and amitriptyline, clomipramine, paroxetine, citalopram or fluoxetine.3 All antidepressants, except fluoxetine, enhanced GR-mediated gene transcription, with clomipramine having the greatest effect (10 fold increase). Twenty-four hours coincubation of cells with desipramine, clomipramine or paroxetine. also enhanced GR function in the presence of cortisol, but not ofcorticosterone.4 It is proposed that these effects are due to the antidepressants inhibiting the L929 membrane steroid transporter, which actively extrudes dexamethasone and cortisol from the cell, but not corticosterone. This is further confirmed by the fact that clomipramine failed to enhance GR-mediated gene transcription in the presence of dexamethasone when the membrane steroid transporter was blocked by verapamil.5 The membrane steroid transporters that regulate access of glucocorticoids to the brain in vivo, like the multiple drug resistance p-glycoprotein, could be a fundamental target for antidepressant action.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 08:05:21