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Titolo:
Impaired activity of the extraneuronal monoamine transporter system known as uptake-2 in Orct3/Slc22a3-deficient mice
Autore:
Zwart, R; Verhaagh, S; Buitelaar, M; Popp-Snijders, C; Barlow, DP;
Indirizzi:
Netherlands Canc Inst, Dept Mol Genet H5, NL-1066 CX Amsterdam, Netherlands Netherlands Canc Inst Amsterdam Netherlands NL-1066 CX rdam, Netherlands Free Univ Amsterdam, Dept Endocrinol, NL-1007 MB Amsterdam, Netherlands Free Univ Amsterdam Amsterdam Netherlands NL-1007 MB terdam, Netherlands
Titolo Testata:
MOLECULAR AND CELLULAR BIOLOGY
fascicolo: 13, volume: 21, anno: 2001,
pagine: 4188 - 4196
SICI:
0270-7306(200107)21:13<4188:IAOTEM>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORGANIC CATION TRANSPORTER; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; 1-METHYL-4-PHENYLPYRIDINIUM MPP+; NORADRENALINE TRANSPORT; MOUSE; NOREPINEPHRINE; EXPRESSION; CELLS; GENE; TRANSMITTERS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Barlow, DP OAW Inst Mol Biol, Billrothstr 11, A-5020 Salzburg, Austria OAWInst Mol Biol Billrothstr 11 Salzburg Austria A-5020 stria
Citazione:
R. Zwart et al., "Impaired activity of the extraneuronal monoamine transporter system known as uptake-2 in Orct3/Slc22a3-deficient mice", MOL CELL B, 21(13), 2001, pp. 4188-4196

Abstract

Two uptake systems that control the extracellular concentrations of released monoamine neurotransmitters such as noradrenaline and adrenaline have been described. Uptake-1 is present at presynaptic nerve endings, whereas uptake-2 is extraneuronal and has been identified in myocardium and vascular and nonvascular smooth muscle cells. The gene encoding the uptake-2 transporter has recently been identified in humans (EMT), rats (OCT3), and mice (Orct3/Slc22a3). To generate an in vivo model for uptake-2, we have inactivated the mouse Orct3 gene. Homozygous mutant mice are viable and fertile with no obvious physiological defect nd also show no significant imbalance of noradrenaline or dopamine. However, Orct3-null mice show an impaired uptake-2activity as measured by accumulation of intravenously administered [H-3]MPP+ (1-methyl-4-phenylpyridinium). A 72% reduction in MPP+ levels was measured in hearts of both male and female Orct3 mutant mice. No significant differences between wild-type and mutant mice were found in any other adult organ or in plasma. When [H-3]MPP+ was injected into pregnant females, a threefold-reduced MPP+ accumulation was observed in homozygous mutant embryos but not in their placentas or amniotic fluid. These data show that Orct3 is the principal component for uptake-2 function in the adult heart and identify the placenta as a novel site of action of uptake-2 that acts at the fetoplacental interface.

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Documento generato il 30/05/20 alle ore 15:08:50