Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Transporter-mediated release: A superfusion study on human embryonic kidney cells stably expressing the human serotonin transporter
Autore:
Scholze, P; Zwach, J; Kattinger, A; Pifl, C; Singer, EA; Sitte, HH;
Indirizzi:
Univ Vienna, Dept Pharmacol, A-1090 Vienna, Austria Univ Vienna Vienna Austria A-1090 Dept Pharmacol, A-1090 Vienna, Austria Univ Vienna, Brain Res Inst, A-1090 Vienna, Austria Univ Vienna Vienna Austria A-1090 Brain Res Inst, A-1090 Vienna, Austria
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 293, anno: 2000,
pagine: 870 - 878
SICI:
0022-3565(200006)293:3<870:TRASSO>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
VESICULAR MONOAMINE TRANSPORTER; RAT HIPPOCAMPAL SYNAPTOSOMES; D-FENFLURAMINE; DOPAMINE TRANSPORTER; HUMAN NORADRENALINE; AMPHETAMINE; COCAINE; EFFLUX; 5-HYDROXYTRYPTAMINE; NEUROTRANSMITTERS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Sitte, HH Univ Vienna, Dept Pharmacol, Waehringerstr 13A, A-1090 Vienna, Austria Univ Vienna Waehringerstr 13A Vienna Austria A-1090 na, Austria
Citazione:
P. Scholze et al., "Transporter-mediated release: A superfusion study on human embryonic kidney cells stably expressing the human serotonin transporter", J PHARM EXP, 293(3), 2000, pp. 870-878

Abstract

HEK 293 cells stably expressing the human serotonin transporter (hSERT) were grown on coverslips, preincubated with [H-3]5-hydroxytryptamine (5-HT), and superfused. Substrates of the hSERT [e.g., p-chloroamphetamine (PCA)], increased the basal efflux of [H-3]5-HT in a concentration-dependent manner. 5-HT reuptake blockers (e.g., imipramine, paroxetine) also raised [H-3]5-HT efflux, reaching approximately one-third of the maximal effect of the hSERT substrates. In uptake experiments, both groups of substances inhibited [H-3]5-HT uptake. Using the low-affinity substrate [H-3]N-methyl-4-phenylpyridinium (MPP+) to label the cells in superfusion experiments, reuptake inhibitors failed to enhance efflux. Similar results were obtained using humanplacental choriocarcinoma (JAR) cells that constitutively express the hSERT at a low level. By contrast, PCA raised [H-3]MPP+ efflux in both types ofcells, and its effect was inhibited by paroxetine. The addition of the Na+,K+-ATPase inhibitor ouabain (100 mu M) to the superfusion buffer enhanced basal efflux of [H-3]5-HT-loaded hSERT cells by approximately 2-fold; the effect of PCA (10 mu M) was strongly augmented by ouabain, whereas the effect of imipramine was not. The Na+/H+ ionophore monensin (10 mu M) also augmented the effect of PCA on efflux of [H-3]5-HT as well as on efflux of [H-3]MPP+. In [H-3]5-HT-labeled cells, the combination of imipramine and monensin raised [H-3]5-HT efflux to a greater extent than either of the two substances alone. In [H-3]MPP+-labeled cells, imipramine had no effect on its ownand fully reversed the effect of monensin. The results suggest that the [H-3]5-HT efflux caused by uptake inhibitors is entirely due to interrupted high-affinity reuptake, which is ongoing even under superfusion conditions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 15:16:41